Arquivo da tag: Genética

Cientistas americanos conseguem clonar embriões humanos (O Globo)

Trabalho é o primeiro a obter êxito em humanos com a técnica que deu origem à ovelha Dolly

Autores dizem que não se trata de fazer clones humanos, mas sim avançar apenas até a fase de blastocisto para obter as células-tronco

Em 2004, sul-coreano anunciou o mesmo feito mas foi desmentido um ano depois

ROBERTA JANSEN

Publicado:15/05/13 – 16h03; atualizado:15/05/13 – 20h56

Clone de embrião obtido no estudoFoto: DivulgaçãoClone de embrião obtido no estudo Divulgação

OREGON. Dezesseis anos depois da clonagem do primeiro mamífero, a ovelha Dolly, cientistas conseguiram, pela primeira vez, clonar um embrião humano em seus primeiros estágios de desenvolvimento. Os protoembriões foram usados para produzir células-tronco embrionárias — capazes de se transformar em qualquer tecido do corpo —, num avanço bastante significativo e há muito tempo esperado para o tratamento de lesões e doenças graves como Parkinson, esclerose múltipla e problemas cardíacos. Especialistas envolvidos no processo garantem que o objetivo não é clonar seres humanos, mas, sim criar novas terapias personalizadas.

Tanto é assim que os embriões humanos clonados usados na pesquisa foram destruídos em estágios ainda muito iniciais de desenvolvimento, logo depois da extração das células-tronco, e não levados ao crescimento, como no caso da ovelha Dolly e de tantos outros animais clonados depois dela. A técnica usada, no entanto, foi bastante similar à que criou a ovelha. Células da pele de um indivíduo foram colocadas em um óvulo previamente esvaziado de seu material genético e estimuladas a se desenvolver. Quando atingiram a fase de blastocisto, as células-tronco embrionárias foram extraídas e os embriões destruídos. O estudo foi publicado na revista “Cell”.

Conseguir gerar grande quantidade de células-tronco do próprio paciente era uma espécie de Santo Graal da atual ciência médica, como comparou o jornalista Steve Connor, no “Independent”. Embora o procedimento tenha sido feito com animais, até agora nunca tinha sido obtido com material humano, a despeito de inúmeras tentativas. Aparentemente, a dificuldade viria da maior fragilidade do óvulo humano.

Em 2004, um grupo coordenado por Woo Suk Hwang, da Universidade Nacional de Seoul, anunciou ter produzido o primeiro embirão humano clonado e, em seguida, obtido células-tronco embionárias a partir dele. Menos de um ano depois, no entanto, o grupo, que já havia clonado um cachorro, foi acusado de fraude e desmentiu os resultados obtidos. Outros grupos tentaram, mas os embriões não passaram do estágio de 6 a 12 células.

A corrida pela obtenção das células-tronco embrionárias faz todo o sentido. Cultivadas em laboratório, essas células podem dar origem a qualquer tecido do corpo humano. Por isso, em tese ao menos, poderiam curar lesões na medula, recompor órgãos, tratar problemas graves de visão, oferecendo tratamentos inéditos para muitas doenças hoje incuráveis. Como os tecidos seriam feitos a partir do material genético do próprio paciente (que, no caso, cedeu as células de sua pele), não haveria risco algum de rejeição. A medicina personalizada alcançaria o seu ápice.

— Nossa descoberta oferece novas maneiras de gerar células-tronco embrionárias para pacientes com problemas em tecidos e órgãos — afirmou o coordenador do estudo, Shoukhrat Mitalipov, da Universidade de Ciência e Saúde do Oregon, nos EUA, em comunicado oficial sobre o estudo. — Essas células-tronco podem regenerar órgãos ou substituir tecidos danificados, levando à cura de doenças que hoje afetam milhões de pessoas.

O grupo também conseguiu observar a capacidade de diferenciação das células obtidas em tecidos específicos

— Um atento exame das células-tronco obtidas por meio desta técnica demonstrou sua capacidade de se converter, como qualquer célula-tronco embrionária normal, em diferentes tipos de células, entre elas, células nervosas, células do fígado e céluas cardíacas — disse Mitalipov, em entrevista ao “Independent”.

No entanto, o estudo já levanta sérias preocupações éticas, sobretudo em relação à criação de clones humanos. Há o temor de que a técnica seja incorporada às oferecidas por clínicas de fertilização in vitro, como alternativa para casais estéreis, por exemplo. Outros grupos argumentam que é simplesmente antiético manipular embriões humanos.

— A pesquisa tem como único objetivo gerar células-tronco embrionárias para tratar doenças graves; e não aumentar as chances de produzir bebês clonados — garantiu Mitalipov. — Este não é o nosso foco e não acreditamos que nossas descobertas sejam usadas por outros grupos como um avanço na clonagem humana reprodutiva.

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The Ethics of Resurrecting Extinct Species (Science Daily)

Apr. 8, 2013 — At some point, scientists may be able to bring back extinct animals, and perhaps early humans, raising questions of ethics and environmental disruption.

Within a few decades, scientists may be able to bring back the dodo bird from extinction, a possibility that raises a host of ethical questions, says Stanford law Professor Hank Greely. (Credit: Frederick William Frohawk/Public domain image)

Within a few decades, scientists may be able to bring back the dodo bird from extinction, a possibility that raises a host of ethical questions, says Stanford law Professor Hank Greely.

Twenty years after the release ofJurassic Park, the dream of bringing back the dinosaurs remains science fiction. But scientists predict that within 15 years they will be able to revive some more recently extinct species, such as the dodo or the passenger pigeon, raising the question of whether or not they should — just because they can.

In the April 5 issue of Science, Stanford law Professor Hank Greely identifies the ethical landmines of this new concept of de-extinction.

“I view this piece as the first framing of the issues,” said Greely, director of the Stanford Center for Law and the Biosciences. “I don’t think it’s the end of the story, rather I think it’s the start of a discussion about how we should deal with de-extinction.”

In “What If Extinction Is Not Forever?” Greely lays out potential benefits of de-extinction, from creating new scientific knowledge to restoring lost ecosystems. But the biggest benefit, Greely believes, is the “wonder” factor.

“It would certainly be cool to see a living saber-toothed cat,” Greely said. “‘Wonder’ may not seem like a substantive benefit, but a lot of science — such as the Mars rover — is done because of it.”

Greely became interested in the ethics of de-extinction in 1999 when one of his students wrote a paper on the implications of bringing back wooly mammoths.

“He didn’t have his science right — which wasn’t his fault because approaches on how to do this have changed in the last 13 years — but it made me realize this was a really interesting topic,” Greely said.

Scientists are currently working on three different approaches to restore lost plants and animals. In cloning, scientists use genetic material from the extinct species to create an exact modern copy. Selective breeding tries to give a closely-related modern species the characteristics of its extinct relative. With genetic engineering, the DNA of a modern species is edited until it closely matches the extinct species.

All of these techniques would bring back only the physical animal or plant.

“If we bring the passenger pigeon back, there’s no reason to believe it will act the same way as it did in 1850,” said co-author Jacob Sherkow, a fellow at the Stanford Center for Law and the Biosciences. “Many traits are culturally learned. Migration patterns change when not taught from generation to generation.”

Many newly revived species could cause unexpected problems if brought into the modern world. A reintroduced species could become a carrier for a deadly disease or an unintentional threat to a nearby ecosystem, Greely says.

“It’s a little odd to consider these things ‘alien’ species because they were here before we were,” he said. “But the ‘here’ they were in is very different than it is now. They could turn out to be pests in this new environment.”

When asked whether government policies are keeping up with the new threat, Greely answers “no.”

“But that’s neither surprising nor particularly concerning,” he said. “It will be a while before any revised species is going to be present and able to be released into the environment.”

Greely and Sherkow recommend that the government leave de-extinction research to private companies and focus on drafting new regulations. Sherkow says the biggest legal and ethical challenge of de-extinction concerns our own long-lost ancestors.

“Bringing back a hominid raises the question, ‘Is it a person?’ If we bring back a mammoth or pigeon, there’s a very good existing ethical and legal framework for how to treat research animals. We don’t have very good ethical considerations of creating and keeping a person in a lab,” said Sherkow. “That’s a far cry from the type of de-extinction programs going on now, but it highlights the slippery slope problem that ethicists are famous for considering.”

Journal Reference:

  1. J. S. Sherkow, H. T. Greely. What If Extinction Is Not Forever? Science, 2013; 340 (6128): 32 DOI:10.1126/science.1236965

Fetal Exposure to Excessive Stress Hormones in the Womb Linked to Adult Mood Disorders (Science Daily)

Apr. 6, 2013 — Exposure of the developing fetus to excessive levels of stress hormones in the womb can cause mood disorders in later life and now, for the first time, researchers have found a mechanism that may underpin this process, according to research presented April 7 at the British Neuroscience Association Festival of Neuroscience (BNA2013) in London.

(Credit: © Tatyana Gladskih / Fotolia)

The concept of fetal programming of adult disease, whereby the environment experienced in the womb can have profound long-lasting consequences on health and risk of disease in later life, is well known; however, the process that drives this is unclear. Professor Megan Holmes, a neuroendocrinologist from the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science in Scotland (UK), will say: “During our research we have identified the enzyme 11ß-HSD2 which we believe plays a key role in the process of fetal programming.”

Adverse environments experienced while in the womb, such as in cases of stress, bereavement or abuse, will increase levels of glucocorticoids in the mother, which may harm the growing baby. Glucocorticoids are naturally produced hormones and they are also known as stress hormones because of their role in the stress response.

“The stress hormone cortisol may be a key factor in programming the fetus, baby or child to be at risk of disease in later life. Cortisol causes reduced growth and modifies the timing of tissue development as well as having long lasting effects on gene expression,” she will say.

Prof Holmes will describe how her research has identified an enzyme called 11ß-HSD2 (11beta-hydroxysteroid dehydrogenase type 2) that breaks down the stress hormone cortisol to an inactive form, before it can cause any harm to the developing fetus. The enzyme 11ß-HSD2 is present in the placenta and the developing fetal brain where it is thought to act as a shield to protect against the harmful actions of cortisol.

Prof Holmes and her colleagues developed genetically modified mice that lacked 11ß-HSD2 in order to determine the role of the enzyme in the placenta and fetal brain. “In mice lacking the enzyme 11ß-HSD2, fetuses were exposed to high levels of stress hormones and, as a consequence, these mice exhibited reduced fetal growth and went on to show programmed mood disorders in later life. We also found that the placentas from these mice were smaller and did not transport nutrients efficiently across to the developing fetus. This too could contribute to the harmful consequences of increased stress hormone exposure on the fetus and suggests that the placental 11ß-HSD2 shield is the most important barrier.

“However, preliminary new data show that with the loss of the 11ß-HSD2 protective barrier solely in the brain, programming of the developing fetus still occurs, and, therefore, this raises questions about how dominant a role is played by the placental 11ß-HSD2 barrier. This research is currently ongoing and we cannot draw any firm conclusions yet.

“Determining the exact molecular and cellular mechanisms that drive fetal programming will help us identify potential therapeutic targets that can be used to reverse the deleterious consequences on mood disorders. In the future, we hope to explore the potential of these targets in studies in humans,” she will say.

Prof Holmes hopes that her research will make healthcare workers more aware of the fact that children exposed to an adverse environment, be it abuse, malnutrition, or bereavement, are at an increased risk of mood disorders in later life and the children should be carefully monitored and supported to prevent this from happening.

In addition, the potential effects of excessive levels of stress hormones on the developing fetus are also of relevance to individuals involved in antenatal care. Within the past 20 years, the majority of women at risk of premature delivery have been given synthetic glucocorticoids to accelerate fetal lung development to allow the premature babies to survive early birth.

“While this glucocorticoid treatment is essential, the dose, number of treatments and the drug used, have to be carefully monitored to ensure that the minimum effective therapy is used, as it may set the stage for effects later in the child’s life,” Prof Holmes will say.

Puberty is another sensitive time of development and stress experienced at this time can also be involved in programming adult mood disorders. Prof Holmes and her colleagues have found evidence from imaging studies in rats that stress in early teenage years could affect mood and emotional behaviour via changes in the brain’s neural networks associated with emotional processing.

The researchers used fMRI (Functional Magnetic Resonance Imaging) to see which pathways in the brain were affected when stressed, peripubertal rats responded to a specific learned task. [1].

Prof Holmes will say: “We showed that in stressed ‘teenage’ rats, the part of the brain region involved in emotion and fear (known as amygdala) was activated in an exaggerated fashion when compared to controls. The results from this study clearly showed that altered emotional processing occurs in the amygdala in response to stress during this crucial period of development.”

Abstract title: “Perinatal programming of stress-related behaviour by glucocorticoids.” Symposium: “Early life stress and its long-term effects — experimental studies.”

Story Source:

The above story is reprinted from materials provided byBritish Neuroscience Association, via AlphaGalileo.

You Don’t ‘Own’ Your Own Genes: Researchers Raise Alarm About Loss of Individual ‘Genomic Liberty’ Due to Gene Patents (Science Daily)

Mar. 25, 2013 — Humans don’t “own” their own genes, the cellular chemicals that define who they are and what diseases they might be at risk for. Through more than 40,000 patents on DNA molecules, companies have essentially claimed the entire human genome for profit, report two researchers who analyzed the patents on human DNA.

In a new study, researchers report that through more than 40,000 patents on DNA molecules, companies have essentially claimed the entire human genome for profit. (Credit: © X n’ Y hate Z / Fotolia)

Their study, published March 25 in the journal Genome Medicine, raises an alarm about the loss of individual “genomic liberty.”

In their new analysis, the research team examined two types of patented DNA sequences: long and short fragments. They discovered that 41 percent of the human genome is covered by longer DNA patents that often cover whole genes. They also found that, because many genes share similar sequences within their genetic structure, if all of the “short sequence” patents were allowed in aggregate, they could account for 100 percent of the genome.

Furthermore, the study’s lead author, Dr. Christopher E. Mason of Weill Cornell Medical College, and the study’s co-author, Dr. Jeffrey Rosenfeld, an assistant professor of medicine at the University of Medicine & Dentistry of New Jersey and a member of the High Performance and Research Computing Group, found that short sequences from patents also cover virtually the entire genome — even outside of genes.

“If these patents are enforced, our genomic liberty is lost,” says Dr. Mason, an assistant professor of physiology and biophysics and computational genomics in computational biomedicine at the Institute for Computational Biomedicine at Weill Cornell. “Just as we enter the era of personalized medicine, we are ironically living in the most restrictive age of genomics. You have to ask, how is it possible that my doctor cannot look at my DNA without being concerned about patent infringement?”

The U.S. Supreme Court will review genomic patent rights in an upcoming hearing on April 15. At issue is the right of a molecular diagnostic company to claim patents not only on two key breast and ovarian cancer genes — BRCA1 and BRCA2 — but also on any small sequence of code within BRCA1, including a striking patent for only 15 nucleotides.

In its study, the research team matched small sequences within BRCA1 to other genes and found that just this one molecular diagnostic company’s patents also covered at least 689 other human genes — most of which have nothing to do with breast or ovarian cancer; rather, its patents cover 19 other cancers as well as genes involved in brain development and heart functioning.

“This means if the Supreme Court upholds the current scope of the patents, no physician or researcher can study the DNA of these genes from their patients, and no diagnostic test or drug can be developed based on any of these genes without infringing a patent,” says Dr. Mason.

One Patented Sequence Matched More Than 91 Percent of Human Genes

Dr. Mason undertook the study because he realized that his research into brain and cancer disorders inevitably involved studying genes that were protected by patents.

Under U.S. patent law, genes can be patented by those researchers, either at companies or institutions, who are first to find a gene that promises a useful application, such as for a diagnostic test. For example, the patents received by a company in the 1990s on BRCA1 and BRCA2 enables it to offer a diagnostic test to women who may have, or may be at risk for, breast or ovarian cancer due to mutations in one or both of these genes. Women and their doctors have no choice but to use the services of the patents’ owner, which costs $3,000 per test, “whereas any of the hundreds of clinical laboratories around the country could perform such a test for possibly much less,” says Dr. Mason.

The impact on these patents is equally onerous on research, Dr. Mason adds.

“Almost every day, I come across a gene that is patented — a situation that is common for every geneticist in every lab,” says Dr. Mason.

Dr. Mason and his research partner sought to determine how many other genes may be impacted by gene patents, as well as the overall landscape of intellectual property on the human genome.

To conduct the study, Dr. Mason and Dr. Rosenfeld examined the structure of the human genome in the context of two types of patented sequences: short and long fragments of DNA. They used matches to known genes that were confirmed to be present in patent claims, ranging from as few as 15 nucleotides (the building blocks of DNA) to the full length of all patented DNA fragments.

Before examining the patented sequences, the researchers first calculated how many genes had common segments of 15 nucleotide (15mer), and found that every gene in the human genome matched at least one other gene in this respect, ranging from as few as five matches 15mer to as many as 7,688 gene matches. They also discovered that 99.999 percent of 15mers in the human genome are repeated at least twice.

“This demonstrates that short patent sequences are extremely non-specific and that a 15mer claim from one gene will always cross-match and patent a portion of another gene as well,” says Dr. Mason. “This means it is actually impossible to have a 15mer patent for just one gene.”

Next, researchers examined the total sequence space in human genes covered by 15mers in current patent claims. They found 58 patents whose claims covered at least 10 percent of all bases of all human genes. The broadest patent claimed sequences that matched 91.5 percent of human genes. Then, when they took existing gene patents and matched patented 15mers to known genes, they discovered that 100 percent of known genes are patented.

“There is a real controversy regarding gene ownership due to the overlap of many competing patent claims. It is unclear who really owns the rights to any gene,” says Dr. Rosenfeld. “While the Supreme Court is hearing one case concerning just the BRCA1 patent, there are also many other patents whose claims would cover those same genes. Do we need to go through every gene to look at who made the first claim to that gene, even if only one small part? If we resort to this rule, then the first patents to be granted for any DNA will have a vast claim over portions of the human genome.”

A further issue of concern is that patents on DNA can readily cross species boundaries. A company can have a patent that they received for cow breeding and have that patent cover a large percentage of human genes. Indeed, the researchers found that one company owns the rights to 84 percent of all human genes for a patent they received for cow breeding. “It seems silly that a patent designed to study cow genetics also claims the majority of human genes,” says Dr. Rosenfeld.

Finally, they also examined the impact of longer claimed DNA sequences from existing gene patents, which ranged from a few dozen bases up to thousands of bases of DNA, and found that these long, claimed sequences matched 41 percent (9,361) of human genes. Their analysis concluded that almost all clinically relevant genes have already been patented, especially for short sequence patents, showing all human genes are patented many times over.

“This is, so to speak, patently ridiculous,” adds Dr. Mason. “If patent claims that use these small DNA sequences are upheld, it could potentially create a situation where a piece of every gene in the human genome is patented by a phalanx of competing patents.”

In their discussion, the researchers argue that the U.S. Supreme Court now has a chance to shape the balance between the medical good versus inventor protection, adding that, in their opinion, the court should limit the patenting of existing nucleotide sequences, due to their broad scope and non-specificity in the human genome.

“I am extremely pro-patent, but I simply believe that people should not be able to patent a product of nature,” Dr. Mason says. “Moreover, I believe that individuals have an innate right to their own genome, or to allow their doctor to look at that genome, just like the lungs or kidneys. Failure to resolve these ambiguities perpetuates a direct threat to genomic liberty, or the right to one’s own DNA.”

Journal Reference:

  1. Jeffrey Rosenfeld, and Christopher E Mason. Pervasive sequence patents cover the entire human genome.Genome Medicine, 2013 (in press) DOI: 10.1186/gm431

DNA Damage Occurs as Part of Normal Brain Activity, Scientists Discover (Science Daily)

Mar. 24, 2013 — Scientists at the Gladstone Institutes have discovered that a certain type of DNA damage long thought to be particularly detrimental to brain cells can actually be part of a regular, non-harmful process. The team further found that disruptions to this process occur in mouse models of Alzheimer’s disease — and identified two therapeutic strategies that reduce these disruptions.

Neurons. Scientists have discovered that a certain type of DNA damage long thought to be particularly detrimental to brain cells can actually be part of a regular, non-harmful process. (Credit: © Roberto Robuffo / Fotolia)

Scientists have long known that DNA damage occurs in every cell, accumulating as we age. But a particular type of DNA damage, known as a double-strand break, or DSB, has long been considered a major force behind age-related illnesses such as Alzheimer’s. Today, researchers in the laboratory of Gladstone Senior Investigator Lennart Mucke, MD, report in Nature Neuroscience that DSBs in neuronal cells in the brain can also be part of normal brain functions such as learning — as long as the DSBs are tightly controlled and repaired in good time. Further, the accumulation of the amyloid-beta protein in the brain — widely thought to be a major cause of Alzheimer’s disease — increases the number of neurons with DSBs and delays their repair.

“It is both novel and intriguing team’s finding that the accumulation and repair of DSBs may be part of normal learning,” said Fred H. Gage, PhD, of the Salk Institute who was not involved in this study. “Their discovery that the Alzheimer’s-like mice exhibited higher baseline DSBs, which weren’t repaired, increases these findings’ relevance and provides new understanding of this deadly disease’s underlying mechanisms.”

In laboratory experiments, two groups of mice explored a new environment filled with unfamiliar sights, smells and textures. One group was genetically modified to simulate key aspects of Alzheimer’s, and the other was a healthy, control group. As the mice explored, their neurons became stimulated as they processed new information. After two hours, the mice were returned to their familiar, home environment.

The investigators then examined the neurons of the mice for markers of DSBs. The control group showed an increase in DSBs right after they explored the new environment — but after being returned to their home environment, DSB levels dropped.

“We were initially surprised to find neuronal DSBs in the brains of healthy mice,” said Elsa Suberbielle, DVM, PhD, Gladstone postdoctoral fellow and the paper’s lead author. “But the close link between neuronal stimulation and DSBs, and the finding that these DSBs were repaired after the mice returned to their home environment, suggest that DSBs are an integral part of normal brain activity. We think that this damage-and-repair pattern might help the animals learn by facilitating rapid changes in the conversion of neuronal DNA into proteins that are involved in forming memories.”

The group of mice modified to simulate Alzheimer’s had higher DSB levels at the start — levels that rose even higher during neuronal stimulation. In addition, the team noticed a substantial delay in the DNA-repair process.

To counteract the accumulation of DSBs, the team first used a therapeutic approach built on two recent studies — one of which was led by Dr. Mucke and his team — that showed the widely used anti-epileptic drug levetiracetam could improve neuronal communication and memory in both mouse models of Alzheimer’s and in humans in the disease’s earliest stages. The mice they treated with the FDA-approved drug had fewer DSBs. In their second strategy, they genetically modified mice to lack the brain protein called tau — another protein implicated in Alzheimer’s. This manipulation, which they had previously found to prevent abnormal brain activity, also prevented the excessive accumulation of DSBs.

The team’s findings suggest that restoring proper neuronal communication is important for staving off the effects of Alzheimer’s — perhaps by maintaining the delicate balance between DNA damage and repair.

“Currently, we have no effective treatments to slow, prevent or halt Alzheimer’s, from which more than 5 million people suffer in the United States alone,” said Dr. Mucke, who directs neurological research at Gladstone and is a professor of neuroscience and neurology at the University of California, San Francisco, with which Gladstone is affiliated. “The need to decipher the causes of Alzheimer’s and to find better therapeutic solutions has never been more important — or urgent. Our results suggest that readily available drugs could help protect neurons against some of the damages inflicted by this illness. In the future, we will further explore these therapeutic strategies. We also hope to gain a deeper understanding of the role that DSBs play in learning and memory — and in the disruption of these important brain functions by Alzheimer’s disease.”

Other scientists who participated in this research at Gladstone include Pascal Sanchez, PhD, Alexxai Kravitz, PhD, Xin Wang, Kaitlyn Ho, Kirsten Eilertson, PhD, Nino Devidze, PhD, and Anatol Kreitzer, PhD. This research was supported by grants from the National Institutes of Health and the S.D. Bechtel, Jr. Foundation.

Journal Reference:

  1. Elsa Suberbielle, Pascal E Sanchez, Alexxai V Kravitz, Xin Wang, Kaitlyn Ho, Kirsten Eilertson, Nino Devidze, Anatol C Kreitzer, Lennart Mucke. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-βNature Neuroscience, 2013; DOI: 10.1038/nn.3356

Pioneiro da epigenética fala sobre relação entre ambiente e genoma (Fapesp)

Moshe Szyf, da Universidade McGill, participa de simpósio internacional organizado pela FAPESP e pela Natura. Discussões do evento embasarão edital para a criação de centros de pesquisa (foto: Edu César)

Especiais
14/03/2013

Por Karina Toledo

Agência FAPESP – Um dos primeiros cientistas a sugerir que os hábitos de vida e o ambiente social em que uma pessoa está inserida poderiam modular o funcionamento de seus genes foi Moshe Szyf, professor de Farmacologia e Terapêutica da Universidade McGill, no Canadá.

Szyf também foi pioneiro ao afirmar que essa programação do genoma – que ocorre por meio de processos bioquímicos batizados de mecanismos epigenéticos – seria um processo fisiológico, uma espécie de resposta adaptativa ao ambiente que começa ainda na vida uterina.

Entre os mecanismos epigenéticos conhecidos, o mais comum e o mais estudado por Szyf é a metilação do DNA, que ocorre quando um conjunto de partículas de hidrogênio e carbono se agrupa na base de alguns genes e impede que eles se expressem.

Embora o processo seja fisiológico, pode se tornar patológico quando acontece no contexto errado. Por exemplo, quando os genes que deveriam nos proteger contra o câncer são desligados.

Pesquisas realizadas pelo grupo de Szyf e colaboradores nos últimos anos mostraram que o padrão de metilação do DNA pode ser alterado por fatores como a qualidade do cuidado materno nos primeiros anos de vida ou a exposição a maus-tratos na infância, criando marcas epigenéticas que perduram ao longo da vida.

Os resultados de alguns desses estudos foram apresentados por Szyf durante o Simpósio Internacional Integração Corpo-Mente-Meio, realizado na sede da FAPESP no dia 12 de março, em parceria com a Natura.

Em um trabalho de 2004, feito com o neurocientista Michael Meaney, também da Universidade McGill, foram comparados dois grupos de ratas: aquelas que tinham recebido lambidas frequentes de suas mães quando ainda eram bebês e aquelas que não haviam recebido cuidados maternos.

Os resultados mostraram que os animais lambidos pelas mães se tornaram adultos mais tranquilos. Isso porque o amor materno alterou os níveis de metilação nas regiões do hipocampo que regulam o gene do receptor de glicocorticoides, ou seja, alteraram a regulação dos níveis de hormônios do estresse durante toda a vida adulta.

Para mostrar que essa lógica se aplicava também a humanos, os pesquisadores da McGill se associaram ao Instituto Universitário de Saúde Mental Douglas, também do Canadá, e ao Instituto de Ciências Clínicas de Cingapura, para analisar cérebros de vítimas de suicídio.

Por meio de seus históricos médicos e de entrevistas com familiares, foi possível identificar entre os suicidas aqueles que tinham sofrido abuso severo durante a infância – seja verbal, sexual ou físico.

Os pesquisadores viram que nesse grupo que teve uma infância difícil os genes que regulam os receptores de glicocorticoides estavam 40% menos ativos quando comparados aos dos suicidas que não sofreram abuso e também quando comparados aos do grupo controle (pessoas que morreram por outras causas, como acidentes de carro).

Os resultados sugerem, portanto, que o abuso infantil deixou essas pessoas mais sensíveis aos danos causados pelo estresse no cérebro; eles foram publicados em 2009 na revista Nature Neuroscience.

Em outros estudos apresentados durante o evento, o cientista mostrou que o padrão de expressão dos genes também pode ser influenciado pela condição socioeconômica na infância e pelo estresse vivenciado pela mãe durante a gestação.

“O avanço no conhecimento sobre a relação entre o ambiente e o genoma ajuda a combater o determinismo genético, ou seja, aquela ideia de que, se você nasce com genes da inteligência, você será inteligente, e se você nasce com genes saudáveis, você será saudável, não importa o que você faça a respeito. Isso coloca mais peso em nossas escolhas. Mostra que temos controle enquanto pais, enquanto formuladores de políticas públicas e enquanto sociedade. Isso pode definir novos modelos para políticas públicas”, disse Szyf à Agência FAPESP.

Para o pesquisador, muitas coisas na prática médica e no cotidiano têm sido feitas sem levar em conta as consequências disso no futuro, mas o avanço no conhecimento sobre a epigenética deve mudar a atitude das pessoas.

“Quando eu era um jovem pai, a ideia predominante era deixar a criança chorar para ela aprender a se virar sozinha. Hoje não fazemos isso porque temos medo do estresse que isso vai causar e de suas consequências. Da mesma forma, temos feito fertilização in vitro, barriga de aluguel, cesarianas desnecessárias sem pensar muito sobre as consequências disso para a criança. Precisamos começar a avaliar o custo-benefício e tomar decisões conscientes, com base em informações”, defendeu.

No campo da medicina, a epigenética traz outras implicações importantes. Uma delas é a possibilidade de identificar biomarcadores que permitam identificar a população mais vulnerável a desenvolver doenças como câncer, infarto, pressão alta ou transtornos mentais.

“O maior desafio é encontrar formas de intervir antes que os sinais clínicos apareçam e a situação se deteriore. Por isso, é tão importante entender o que torna as pessoas vulneráveis. Esse conhecimento também vai nos guiar quanto ao tipo de intervenção mais adequada”, disse.

No rol das intervenções epigenéticas possíveis, afirmou Szyf, estão as drogas capazes de reverter as alterações no padrão de expressão dos genes – algo que já é feito na área de oncologia e começa a ser testado na área psiquiátrica.

Intervenções epigenéticas podem ser feitas também por meio de psicoterapia ou de políticas públicas que promovam a mudança do comportamento. “A grande revolução virá quando aprendermos como nos comportar para atingir o mesmo efeito que as drogas são capazes de promover. Descobrir como intervir no sistema de forma que se possa reverter adaptações epigenéticas adversas unicamente pelo comportamento”, afirmou.

Parceria entre FAPESP e Natura

O Simpósio Internacional Integração Corpo-Mente-Meio também contou com a participação do professor Paul Rozin, da Universidade da Pennsylvania (Estados Unidos), que falou sobre as perspectivas na área de Psicologia Positiva – definida como o estudo das forças e virtudes que permitem aos indivíduos e às comunidades prosperar.

Também participaram os brasileiros Silvia Koller, da Universidade Federal do Rio Grande do Sul (UFRGS), Mirian Galvonas Jasiulionis, da Universidade Federal de São Paulo (Unifesp), e Edson Amaro Júnior, da Faculdade de Medicina da Universidade de São Paulo (FMUSP). Respectivamente, eles apresentaram o cenário nacional das pesquisas em Psicologia Positiva, Epigenética e Neurociências.

Segundo o diretor científico da FAPESP, Carlos Henrique de Brito Cruz, as discussões do evento vão embasar a elaboração de um edital que será lançado pela Fundação e pela Natura para a criação de um ou mais centros de pesquisa nos moldes do CEPID (Centros de Pesquisa, Inovação e Difusão), caso em que o financiamento pode durar até dez anos.

“Queremos aprender mais sobre os desafios relacionados a esses temas para que possamos definir como será o financiamento, qual é a melhor forma de montar a armadilha para o conhecimento e obter bons resultados. Nem sempre é simples acertar o relacionamento entre as pessoas das universidades e as pessoas das empresas. Sempre há objetivos não convergentes. Nossa tarefa é achar as convergências possíveis”, afirmou Brito Cruz.

Além do diretor científico da FAPESP, também participou da abertura do evento o diretor de Ciência e Tecnologia da Natura, Victor Fernandes. “Estamos aqui tentando entender qual é a interface científica entre três ciências muito relevantes: Neurosciência Comportamental, Psicologia Positiva e Epigenética. O objetivo é entender como o comportamento e o cotidiano influenciam o comportamento biológico e, em cima disso, buscar oportunidades de fomento à ciência e à inovação”, destacou.

Some Plants Are Altruistic, Too, New Study Suggests (Science Daily)

Feb. 1, 2013 — We’ve all heard examples of animal altruism: Dogs caring for orphaned kittens, chimps sharing food or dolphins nudging injured mates to the surface. Now, a study led by the University of Colorado Boulder suggests some plants are altruistic too.

A new study led by CU-Boulder involving graduate student Chi-Chih Wu, shown here, indicates corn plants may have an altruistic side. (Credit: Photo courtesy CU-Boulder)

The researchers looked at corn, in which each fertilized seed contained two “siblings” — an embryo and a corresponding bit of tissue known as endosperm that feeds the embryo as the seed grows, said CU-Boulder Professor Pamela Diggle. They compared the growth and behavior of the embryos and endosperm in seeds sharing the same mother and father with the growth and behavior of embryos and endosperm that had genetically different parents.

“The results indicated embryos with the same mother and father as the endosperm in their seed weighed significantly more than embryos with the same mother but a different father,” said Diggle, a faculty member in CU-Boulder’s ecology and evolutionary biology department. “We found that endosperm that does not share the same father as the embryo does not hand over as much food — it appears to be acting less cooperatively.”

A paper on the subject was published during the week of Jan. 21 in the Proceedings of the National Academy of Sciences. Co-authors on the study included Chi-Chih Wu, a CU-Boulder doctoral student in the ecology and evolutionary biology department and Professor William “Ned” Friedman, a professor at Harvard University who helped conduct research on the project while a faculty member at CU-Boulder.

Diggle said it is fairly clear from previous research that plants can preferentially withhold nutrients from inferior offspring when resources are limited. “Our study is the first to specifically test the idea of cooperation among siblings in plants.”

“One of the most fundamental laws of nature is that if you are going to be an altruist, give it up to your closest relatives,” said Friedman. “Altruism only evolves if the benefactor is a close relative of the beneficiary. When the endosperm gives all of its food to the embryo and then dies, it doesn’t get more altruistic than that.”

In corn reproduction, male flowers at the top of the plants distribute pollen grains two at a time through individual tubes to tiny cobs on the stalks covered by strands known as silks in a process known as double fertilization. When the two pollen grains come in contact with an individual silk, they produce a seed containing an embryo and endosperm. Each embryo results in just a single kernel of corn, said Diggle.

The team took advantage of an extremely rare phenomenon in plants called “hetero-fertilization,” in which two different fathers sire individual corn kernels, said Diggle, currently a visiting professor at Harvard. The manipulation of corn plant genes that has been going on for millennia — resulting in the production of multicolored “Indian corn” cobs of various colors like red, purple, blue and yellow — helped the researchers in assessing the parentage of the kernels, she said.

Wu, who cultivated the corn and harvested more than 100 ears over a three-year period, removed, mapped and weighed every individual kernel out of each cob from the harvests. While the majority of kernels had an endosperm and embryo of the same color — an indication they shared the same mother and father — some had different colors for each, such as a purple outer kernel with yellow embryo.

Wu was searching for such rare kernels — far less than one in 100 — that had two different fathers as a way to assess cooperation between the embryo and endosperm. “It was very challenging and time-consuming research,” said Friedman. “It was like looking for a needle in a haystack, or in this case, a kernel in a silo.”

Endosperm — in the form of corn, rice, wheat and other crops — is critical to humans, providing about 70 percent of calories we consume annually worldwide. “The tissue in the seeds of flowering plants is what feeds the world,” said Friedman, who also directs the Arnold Arboretum at Harvard. “If flowering plants weren’t here, humans wouldn’t be here.”

Journal Reference:

  1. K. Baruch, N. Ron-Harel, H. Gal, A. Deczkowska, E. Shifrut, W. Ndifon, N. Mirlas-Neisberg, M. Cardon, I. Vaknin, L. Cahalon, T. Berkutzki, M. P. Mattson, F. Gomez-Pinilla, N. Friedman, M. Schwartz. CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging.Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1211270110

Scientists discover how epigenetic information could be inherited (University of Cambridge)

Public release date: 24-Jan-2013
By Genevieve Maul

Research reveals the mechanism of epigenetic reprogramming

New research reveals a potential way for how parents’ experiences could be passed to their offspring’s genes. The research was published today, 25 January, in the journal Science.

Epigenetics is a system that turns our genes on and off. The process works by chemical tags, known as epigenetic marks, attaching to DNA and telling a cell to either use or ignore a particular gene.

The most common epigenetic mark is a methyl group. When these groups fasten to DNA through a process called methylation they block the attachment of proteins which normally turn the genes on. As a result, the gene is turned off.

Scientists have witnessed epigenetic inheritance, the observation that offspring may inherit altered traits due to their parents’ past experiences. For example, historical incidences of famine have resulted in health effects on the children and grandchildren of individuals who had restricted diets, possibly because of inheritance of altered epigenetic marks caused by a restricted diet.

However, it is thought that between each generation the epigenetic marks are erased in cells called primordial gene cells (PGC), the precursors to sperm and eggs. This ‘reprogramming’ allows all genes to be read afresh for each new person – leaving scientists to question how epigenetic inheritance could occur.

The new Cambridge study initially discovered how the DNA methylation marks are erased in PGCs, a question that has been under intense investigation over the past 10 years. The methylation marks are converted to hydroxymethylation which is then progressively diluted out as the cells divide. This process turns out to be remarkably efficient and seems to reset the genes for each new generation. Understanding the mechanism of epigenetic resetting could be exploited to deal with adult diseases linked with an accumulation of aberrant epigenetic marks, such as cancers, or in ‘rejuvenating’ aged cells.

However, the researchers, who were funded by the Wellcome Trust, also found that some rare methylation can ‘escape’ the reprogramming process and can thus be passed on to offspring – revealing how epigenetic inheritance could occur. This is important because aberrant methylation could accumulate at genes during a lifetime in response to environmental factors, such as chemical exposure or nutrition, and can cause abnormal use of genes, leading to disease. If these marks are then inherited by offspring, their genes could also be affected.

Dr Jamie Hackett from the University of Cambridge, who led the research, said: “Our research demonstrates how genes could retain some memory of their past experiences, revealing that one of the big barriers to the theory of epigenetic inheritance – that epigenetic information is erased between generations – should be reassessed.”

“It seems that while the precursors to sperm and eggs are very effective in erasing most methylation marks, they are fallible and at a low frequency may allow some epigenetic information to be transmitted to subsequent generations. The inheritance of differential epigenetic information could potentially contribute to altered traits or disease susceptibility in offspring and future descendants.”

“However, it is not yet clear what consequences, if any, epigenetic inheritance might have in humans. Further studies should give us a clearer understanding of the extent to which heritable traits can be derived from epigenetic inheritance, and not just from genes. That could have profound consequences for future generations.”

Professor Azim Surani from the University of Cambridge, principal investigator of the research, said: “The new study has the potential to be exploited in two distinct ways. First, the work could provide information on how to erase aberrant epigenetic marks that may underlie some diseases in adults. Second, the study provides opportunities to address whether germ cells can acquire new epigenetic marks through environmental or dietary influences on parents that may evade erasure and be transmitted to subsequent generations, with potentially undesirable consequences.”

We Are All Mosaics (National Geographic)

by Virginia Hughes, 21 December 2012

Here’s something you probably learned once in a biology class, more or less. There’s this molecule called DNA. It contains a long code that created you and is unique to you. And faithful copies of the code live inside the nucleus of every one of the trillions of cells in your body.

In a later class you may have learned a few exceptions to that “faithful copies” bit. Sometimes, especially during development, when cells are dividing into more cells, a mutation pops up in the DNA of a daughter cell. This makes the daughter cell and all of its progeny genetically distinct. The phenomenon is called ‘somatic mosaicism’, and it tends to happen in sperm cells, egg cells, immune cells, and cancer cells. But it’s pretty infrequent and, for most healthy people, inconsequential.

That’s what the textbooks say, anyway, and it’s also a common assumption in medical research. For instance, genetic studies of living people almost always collect DNA from blood draws or cheek swabs, even if investigating the tangled roots of, say, heart disease or diabetes or autism. The assumption is that whatever genetic blips show up in blood or saliva will recapitulate what’s in the (far less accessible) cells of the heart, pancreas, or brain.

Two recent reports suggest that somatic mosaicism is far more common than anybody ever realized — and that might be a good thing.

 

Colored bars show the locations of genetic glitches in tissues from each of the six subjects (inner vertical numbers). The numbers on the outer edge of the circle correspond to each of our 23 chromosomes, and each color represents a different organ. Image courtesy of PNAS

In the first study Michael Snyder and colleagues looked at cells in 11 different organs and tissues obtained from routine autopsies of six unrelated people who had not died of cancer or any hereditary disease.

Then the scientists screened each tissue for small deletions or duplications of DNA, called copy number variations, or CNVs. These are fairly common in all of us.

In order to do genetic screens, researchers have to mash up a bunch of cells and pull DNA out of the aggregate. That makes research on somatic mutations tricky, because you can’t tell how some cells in the tissue might be different from others. The researchers got around that problem by doing side-by-side comparisons of the tissues from each person. If one tissue has a CNV and the other one doesn’t, they reasoned, then it must be a somatic glitch.

As they reported in October in the Proceedings of the National Academy of Sciences, Snyder’s team found a total of 73 somatic CNVs in the six people, cropping up in tissues all over the body, including the brain, liver, pancreas and small intestine. “Your genome is not static — it does change through development,” says Snyder, chair of the genetics department at Stanford. “People knew that, but it had never been systematically studied.”

OK, but do somatic mutations do anything? It’s hard to tell, particularly because postmortem studies offer no living person to observe. Still, the scientists showed that 79 percent of the somatic mutations fell inside of genes, and most of those genes play a role in the cell’s everyday regulatory processes, like metabolism, phosphorylation, and turning genes on. So the somatic mutations could very well have had an impact.

In the last paragraph of their paper the researchers mention that the findings could also have big implications for studies of induced pluripotent stem (iPS) cells. This line of research is getting increasingly popular, for good reason. With iPS technology, researchers start with a small piece of skin (or…) from a living person. They then expose those skin cells to a certain chemical concoction that reprograms them back into a primordial state. Once the stem cells are created, researchers can put them in yet another chemical soup that coaxes them to differentiate into whatever type of cell the scientists want to study. You can see why it’s cool: The technique allows scientists to create cells — each holding an individual’s unique DNA code, remember — in a Petri dish. Researchers can study neurons of children with autism, for example, without ever touching their brains.

Trouble is, several groups have reported that iPS cells carry mutations that the original skin cells don’t have. This suggests that something screwy is happening during the reprogramming process, defeating the whole purpose of making the cells. (Fellow Phenomena contributor Ed Yong wrote a fantastic post about the hoopla last year.)

But that last paragraph of Snyder’s study offers a bit of hope. What if the mutations that crop up in iPS cells actually were in the skin cells they came from, but just didn’t get picked up because those skin cells were mixed with other skin cells that didn’t have the mutations? In other words, what if skin cells, like all those other tissues they looked at in the paper, are mosaics?

The second new study, published last month in Naturefinds exactly that.

Flora Vaccarino‘s team at Yale sequenced the entire genome of 21 iPS cell lines, three each from seven people, as well as the skin cells that the iPS cells originated from. It turns out that each iPS line has an average of two CNVs and that at least half of these come from somatic mutations in the skin cells. (The researchers used special techniques for amplifying the DNA of the skin cells, so that they could detect CNVs that are present only in a fraction of the cells.)

That means two things. First, researchers using iPS cells can exhale. Their freaky reprogramming process doesn’t seem to create too much genetic havoc in the iPS cells. And second, somatic mosaicism happens a lot. Vaccarino’s study estimates that a full 30 percent of the skin cells carry somatic mutations.

Our widespread mosaicism may have implications for certain diseases. Somatic mutations have been strongly linked to tumors, for example, so it could be that people who have a lot of mosaicism are at a higher risk of cancer. But there’s also a positive way to spin it. Somatic mutations give our genomes an extra layer of flexibility, in a sense, that can come in handy. Snyder gives a good example in his study. If you have a group of cells that are constantly exposed to viruses, say, then it might be beneficial to have a somatic mutation pop up that damages receptors on the cell that viruses can latch on to.

But there’s likely a more parsimonious explanation for all of those genetic copying mistakes. “When you’re replicating DNA, there’s a certain expense to keep everything perfect,” Snyder says, meaning that it would cost the cell a lot of energy to ensure that every new cell was identical to the last. And in the end, he adds, that extra expense may not be worth it. “Having imperfections could just be an economically beneficial way for organisms to do things.”

Photos from Shannon O’Hara and James Diin, courtesy of National Geographic’s My Shot

Bullying by Childhood Peers Leaves a Trace That Can Change the Expression of a Gene Linked to Mood (Science Daily)

Dec. 18, 2012 — A recent study by a researcher at the Centre for Studies on Human Stress (CSHS) at the Hôpital Louis-H. Lafontaine and professor at the Université de Montréal suggests that bullying by peers changes the structure surrounding a gene involved in regulating mood, making victims more vulnerable to mental health problems as they age.

The study published in the journal Psychological Medicine seeks to better understand the mechanisms that explain how difficult experiences disrupt our response to stressful situations. “Many people think that our genes are immutable; however this study suggests that environment, even the social environment, can affect their functioning. This is particularly the case for victimization experiences in childhood, which change not only our stress response but also the functioning of genes involved in mood regulation,” says Isabelle Ouellet-Morin, lead author of the study.

A previous study by Ouellet-Morin, conducted at the Institute of Psychiatry in London (UK), showed that bullied children secrete less cortisol — the stress hormone — but had more problems with social interaction and aggressive behaviour. The present study indicates that the reduction of cortisol, which occurs around the age of 12, is preceded two years earlier by a change in the structure surrounding a gene (SERT) that regulates serotonin, a neurotransmitter involved in mood regulation and depression.

To achieve these results, 28 pairs of identical twins with a mean age of 10 years were analyzed separately according to their experiences of bullying by peers: one twin had been bullied at school while the other had not. “Since they were identical twins living in the same conditions, changes in the chemical structure surrounding the gene cannot be explained by genetics or family environment. Our results suggest that victimization experiences are the source of these changes,” says Ouellet-Morin. According to the author, it would now be worthwhile to evaluate the possibility of reversing these psychological effects, in particular, through interventions at school and support for victims.

Journal Reference:

  1. I. Ouellet-Morin, C. C. Y. Wong, A. Danese, C. M. Pariante, A. S. Papadopoulos, J. Mill, L. Arseneault. Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twinsPsychological Medicine, 2012; DOI: 10.1017/S0033291712002784

Reading history through genetics (Columbia University)

5-Dec-2012, by Holly Evarts

New method analyzes recent history of Ashkenazi and Masai populations, paving the way to personalized medicine

New York, NY—December 5, 2012—Computer scientists at Columbia’s School of Engineering and Applied Science have published a study in the November 2012 issue of The American Journal of Human Genetics (AJHG) that demonstrates a new approach used to analyze genetic data to learn more about the history of populations. The authors are the first to develop a method that can describe in detail events in recent history, over the past 2,000 years. They demonstrate this method in two populations, the Ashkenazi Jews and the Masai people of Kenya, who represent two kinds of histories and relationships with neighboring populations: one that remained isolated from surrounding groups, and one that grew from frequent cross-migration across nearby villages.

“Through this work, we’ve been able to recover very recent and refined demographic history, within the last few centuries, in contrast to previous methods that could only paint broad brushstrokes of the much deeper past, many thousands of years ago,” says Computer Science Associate Professor Itsik Pe’er, who led the research. “This means that we can now use genetics as an objective source of information regarding history, as opposed to subjective written texts.”

Pe’er’s group uses computational genetics to develop methods to analyze DNA sequence variants. Understanding the history of a population, knowing which populations had a shared origin and when, which groups have been isolated for a long time, or resulted from admixture of multiple original groups, and being able to fully characterize their genetics is, he explains, “essential in paving the way for personalized medicine.”

For this study, the team developed the mathematical framework and software tools to describe and analyze the histories of the two populations and discovered that, for instance, Ashkenazi Jews are descendants of a small number—in the hundreds—of individuals from the late medieval times, and since then have remained genetically isolated while their population has expanded rapidly to several millions today.

“Knowing that the Ashkenazi population has expanded so recently from a very small number has practical implications,” notes Pe’er. “If we can obtain data on only a few hundreds of individuals from this population, a perfectly feasible task in today’s technology, we will have effectively collected the genomes of millions of current Ashkenazim.” He and his team are now doing just that, and have already begun to analyze a first group of about 150 Ashkenazi genomes.

The genetic data of the Masai, a semi-nomadic people, indicates the village-by-village structure of their population. Unlike the isolated Ashkenazi group, the Masai live in small villages but regularly interact and intermarry across village boundaries. The ancestors of each village therefore typically come from many different places, and a single village hosts an effective gene pool that is much larger than the village itself.

Previous work in population genetics was focused on mutations that occurred very long ago, say the researchers, and therefore able to only describe population changes that occurred at that timescale, typically before the agricultural revolution. Pe’er’s research has changed that, enabling scientists to learn more about recent changes in populations and start to figure out, for instance, how to pinpoint severe mutations in personal genomes of specific individuals—mutations that are more likely to be associated with disease.

“This is a thrilling time to be working in computational genetics,” adds Pe’er, citing the speed in which data acquisition has been accelerating; much faster than the ability of computing hardware to process such data. “While the deluge of big data has forced us to develop better algorithms to analyze them, it has also rewarded us with unprecedented levels of understanding.”

###

Pe’er’s team worked closely on this research with study co-authors, Ariel Darvasi, PhD of the Hebrew University of Jerusalem, who was responsible for collecting most of the study samples, and Todd Lencz, PhD of Feinstein institute for Medical Research, who handled genotyping of the DNA samples. The team’s computing and analysis took place in the Columbia Initiative in Systems Biology (CISB).

This research is supported by the National Science Foundation (NSF). The computing facility of CISB is supported by the National Institutes of Health (NIH).

Life span of humans took a huge jump in past century (MSNBC)

Researchers credit environmental improvements, not genetics, for the increaseBy Trevor Stokes

updated 10/15/2012 7:11:26 PM ET

Humans are living longer than ever, a life-span extension that occurred more rapidly than expected and almost solely from environmental improvements as opposed to genetics, researchers said Monday.

Four generations ago, the average Swede had the same probability of dying as a hunter-gatherer, but improvements in our living conditions through medicine, better sanitation and clean drinking water (considered “environmental” changes) decreased mortality rates to modern levels in just 100 years, researchers found.

In Japan, 72 has become the new 30, as the likelihood of a 72-year-old modern-day person dying is the same as a 30-year-old hunter-gatherer ancestor who lived 1.3 million years ago. Though the researchers didn’t specifically look at the United States, they say the trends are not country-specific and not based in genetics.

Quick jump in life span
The same progress of decreasing average probability of dying at a certain age in hunters-gatherers that took 1.3 million years to achieve was made in 30 years during the 21st century.

“I pictured a more gradual transition from a hunter-gatherer mortality profile to something like we have today, rather than this big jump, most of which occurred in the last four generations, to me that was surprise,” lead author Oskar Burger, postdoctoral fellow at the Max Planck Institute for Demographic Research in Germany, told LiveScience.

Biologists have lengthened life spans of worms, fruit flies and mice in labs by selectively breeding for old-age survivorship or tweaking their endocrine system, a network of glands that affects every cell in the body. However, the longevity gained in humans over the past four generations is even greater than can be created in labs, researchers concluded. [Extending Life: 7 Ways to Live Past 100]

Genetics vs. environment
In the new work, Burger and colleagues analyzed previously published mortality data from Sweden, France and Japan, from present-day hunter-gatherers and from wild chimpanzees, the closet living relative to humans.

Humans have lived for an estimated 8,000 generations, but only in the past four have mortalities decreased to modern-day levels. Hunter-gatherers today have average life spans on par with wild chimpanzees.

The research suggests that while genetics plays a small role in shaping human mortality, the key in driving up our collective age lies with the advent of medical technologies, improved nutrition, higher education, better housing and several other improvements to the overall standards of living.

“This recent progress has been just astronomically fast compared to what we made since the split from chimpanzees,” Burger said.

Most of the brunt of decreased mortality comes in youth: By age 15, hunters and gatherers have more than 100 times the chance of dying as modern-day people.

What’s next?
“In terms of what’s going on in the next four generations, I want to be very clear that I don’t make any forecasts,” Burger said. “We’re in a period of transition and we don’t know what the new stable point will be.”

However, some researchers say that humans may have maxed out their old age.

“These mortality curves (that show the probability of dying by a certain age), they are now currently at their lowest possible value, which makes a very strong prediction that life span cannot increase much more,” Caleb Finch, a neurogerontology professor at the University of Southern California who studies the biological mechanisms of aging, told LiveScience in an email.

Further, Finch, who was not involved in the current study, argues that environmental degradation, including climate change and ozone pollution, combined with increased obesity “are working to throw us back to an earlier phase of our improvements, they’re regressive.”

“It’s impossible to make any reasonable predictions, but you can look, for example, in local environments in Los Angeles where the density of particles in the air predict the rate of heart disease and cancer,” Finch said, illustrating the link between the environment and health.

The study was detailed Monday in the journal Proceedings of the National Academy of Sciences.

As rotas das suçuaranas (Fapesp)

Felinos conseguem se movimentar em zonas de ocupação humana, mas encontram obstáculos nas estradas

MARIA GUIMARÃES | Edição 199 – Setembro de 2012

A onça-parda (Puma concolor), um dos maiores predadores das Américas, ainda é pouco conhecida pela ciência brasileira. © EDUARDO CESAR (FOTO FEITA NA FUNDAÇÃO ZOOLÓGICO DE SÃO PAULO)

Análises genéticas estão revelando um pouco da história e da ecologia da suçuarana, ou onça-parda (Puma concolor), um dos maiores felinos do Brasil, atrás apenas da onça-pintada. Esses discretos animais são altamente adaptáveis e vivem mesmo em zonas com pouca floresta. Mas enfrentam problemas com a caça e nas estradas, conforme vem mostrando o trabalho paralelo de duas pesquisadoras que nunca se encontraram pessoalmente: Camila Castilho, atualmente na Universidade de São Paulo (USP), e Renata Miotto, agora na Escola Superior de Agricultura Luiz de Queiroz (Esalq), também da USP, em Piracicaba.

As duas estudaram aspectos genéticos de populações locais de suçuaranas, chegando em grande parte a resultados semelhantes, conforme mostram o artigo de Renata naConservation Genetics em 2011, e de Camila publicado este ano na Genetics and Molecular Biology. O primeiro aspecto importante é que há pouca diferenciação genética nas áreas estudadas, sinal de uma população não fragmentada. Isso indica que esses animais conseguem percorrer grandes distâncias e manter o fluxo de material genético, apesar de não haver continuidade de floresta. É bem diferente do que acontece com a onça-pintada, que se aventura pouco fora das áreas de mata e acaba ficando isolada em fragmentos e gerando populações diferenciadas, conforme já mostraram outros estudos.

Na prática, a onça-parda forma populações contínuas ao longo de áreas extensas. No caso de Camila, que desenvolveu o trabalho durante o doutorado pela Universidade Federal do Rio Grande do Sul (UFRGS), a área englobava boa parte de Santa Catarina, uma parte do sul do Paraná e algumas amostras no extremo norte do Rio Grande do Sul, um total de mais de 140 mil quilômetros quadrados (km2). O estudo de Renata, à época doutoranda na Universidade Federal de São Carlos (UFSCar), era mais circunscrito, mas nada diminuto: cerca de 1.700 km2 do interior paulista que incluem 15 municípios, entre eles Ribeirão Preto, Rio Claro e São Carlos.

O outro achado semelhante entre os dois estudos mostra que recentemente, em algum ponto do último século, houve uma drástica redução nos números das suçuaranas, que os geneticistas de populações chamam de gargalo populacional. Ao passar por um desses gargalos, a população perde parte da sua diversidade genética, o que em certos casos pode gerar problemas. “A perda de genes é aleatória e é possível que nada importante se vá”, explica Camila, “mas é maior a probabilidade de acontecer um azar”. Um azar seria o animal não poder contar com algum gene essencial para enfrentar a alterações no ambiente. Uma coisa é certa quando se detecta um gargalo: aconteceu algum desequilíbrio na população, seja uma redução importante em tamanho ou, mais raramente, uma alteração drástica na proporção entre machos e fêmeas.

Canavial

É aí que começam as diferenças entre os dois estudos. O interior de São Paulo, onde Renata trabalha, está recoberto de cana-de-açúcar. “A maior parte foi plantada nos anos 1960 e 1970, em razão do Proálcool [Programa Nacional do Álcool]”, diz a pesquisadora. “Os dados genéticos indicam que o gargalo pode ter acontecido nessa época.” Nesse caso, muitas suçuaranas teriam morrido nesse período de intenso desmatamento, e depois aos poucos a população teria voltado a aumentar, à medida que suas presas se adaptaram a viver nos canaviais. “A dieta das onças na região consiste principalmente em tatus, cervos, capivaras e outros roedores”, conta. São animais que aparentemente vêm se adaptando bem à agricultura, alguns deles consumidores de cana-de-açúcar. Com alimento abundante, as suçuaranas podem facilmente viver na região, sem representar problemas para os donos das plantações.

O grande problema que esses animais enfrentam hoje são as estradas movimentadas, praticamente intransponíveis para pedestres – sejam eles humanos ou felinos –, que cortam o estado. Isso pode bloquear as rotas das suçuaranas e, com o tempo, reduzir a variabilidade genética.

Além de limitar o trânsito das suçuaranas, atropelamentos são uma causa importante de mortalidade. “Os machos jovens, que se dispersam para longe da área onde nasceram, são as principais vítimas”, diz Renata. Entre os 23 animais atropelados de sua amostragem, 16 são machos. A suçuarana Anhanguera, apelidada em 2009 com o nome da estrada em que foi atropelada, no interior paulista, era justamente um macho jovem. “Essa mortalidade diferencial pode alterar a razão sexual, o que pode ser detectado como um gargalo.” Isso acontece porque são eles os emissários do material genético, já que se mudam para uma zona distante onde afinal se estabelecem e acasalam.

As fêmeas permanecem mais próximas ao local onde nasceram, conforme Renata mostrou em cinco anos de monitoramento na Estação Ecológica de Jataí, no município de Luis Antônio, perto de Ribeirão Preto. Ao longo desse período ela percorreu trilhas e coletou fezes frescas, de onde extraiu material genético. Os dados, publicados este ano na Biotropica, mostram que todas as onças residentes são fêmeas.

 

Gado

Na Região Sul, Camila deparou com uma relação mais conflituosa entre os seres humanos e o leão-baio, como o felino é conhecido em terras catarinenses. Ali se criam vários tipos de gado – vacas, cabras, ovelhas – de forma extensiva, com os animais sempre soltos no pasto. Além das pacas, cutias e veados, os animais domésticos acabam virando boas refeições para as suçuaranas, que em seguida precisam enfrentar o fazendeiro armado. “Embora a caça seja ilegal, sabemos que acontece muito nessa região”, conta Camila, que aos poucos venceu as resistências e conseguiu que os donos das fazendas lhe cedessem amostras dos leões-baios caçados, para extração de material genético. A zona de estudo da pesquisadora se concentrou no sul de Santa Catarina, onde as fazendas se estendem por campos de altitude com resquícios de floresta – os capões – em meio ao pasto. É nesses capões, e nas matas ao longo de rios, que as suçuaranas se refugiam e onde por vezes encontram uma cabra ou bezerro também em busca de abrigo.

Assim como em São Paulo, os dados de Camila mostram que o gargalo populacional aconteceu no último século, coincidindo com a ampla derrubada da floresta de araucárias que caracterizava a região. Atualmente, a caça parece ser responsável pela maior parte da mortalidade por ali, e não a falta de hábitat. “Conectividade não parece ser um problema”, comenta Camila. Por meio de modelos ecológicos que analisam a paisagem ela sugere, em artigo de 2011 na Mammalian Biology, que não há impedimento para que esses animais se locomovam por toda a sua área de estudo, que abrange boa parte da Região Sul. Um dado genético que corrobora essa ideia é o baixo parentesco entre os indivíduos que conseguiu analisar. “Apenas 6,6% dos indivíduos que analisamos eram aparentados”, conta. Para ela, é preciso conscientizar os fazendeiros da importância ecológica dos grandes predadores e buscar soluções, como a construção de currais onde o gado possa passar a noite.

Mesmo nunca tendo conversado, as duas pesquisadoras continuam a seguir caminhos paralelos. Ambas, atualmente no pós-doutorado, deixaram a genética de lado para se concentrar na análise da paisagem. “São abordagens complementares”, explica Camila. Diante das informações fornecidas pela distribuição da variação genética, surgiram novas perguntas que as levaram a buscar entender o ambiente por onde as onças-pardas circulam em busca de detectar os problemas que elas enfrentam e propor soluções para manter populações viáveis desse grande felino encontrado em quase toda a América, exceto em boa parte da Argentina e na metade leste da América do Norte.

Agora ambas trabalham em São Paulo: Renata está construindo um banco de dados sobre a cobertura vegetal e a ocupação da mesma região que examinou até o momento, incluindo um mapeamento detalhado da malha viária e do fluxo de veículos, que em conjunto com os dados genéticos formarão um modelo de dispersão. Ao mesmo tempo compila dados de atropelamentos e, com ajuda da Polícia Florestal, aumenta sua coleção de amostras genéticas. “A partir desses modelos, quero avaliar as rotas preferenciais no deslocamento das onças para definir o que se pode fazer em termos de manejo da paisagem”, explica. Camila concentra seu projeto no mosaico das serras da Bocaina e da Mantiqueira, no nordeste paulista, que inclui a região de São José dos Campos. Nessa região, avaliará o hábitat disponível e as possibilidades de locomoção das suçuaranas. “Vou criar valores de permeabilidade para detectar as áreas prioritárias em termos de conservação.”

Em conjunto, os dois projetos podem contribuir para reduzir o desequilíbrio que existe entre a América do Norte e a do Sul no que diz respeito ao conhecimento a respeito desse imponente predador. Talvez também cheguem a propostas de práticas pecuárias que melhorem a convivência entre fazendeiros e predadores, e a passarelas ou túneis para travessia de suçuaranas.

Artigos científicos
CASTILHO, C. S. et alGenetic structure and conservation of Mountain Lions in the South-Brazilian Atlantic Rain ForestGenetics and Molecular Biology. v. 35 (1), p. 65-73. 2012.
CASTILHO, C. S. et alLandscape genetics of mountain lions (Puma concolor) in southern BrazilMammalian Biology. v. 76 (4), p. 476-83. 2011.
MIOTTO, R. A. et alMonitoring a puma (Puma concolor) population in a fragmented landscape in Southeast BrazilBiotropica. v. 44 (1), p. 98-104. 2012.
MIOTTO, R. A. et alGenetic diversity and population structure of pumas (Puma concolor) in southeastern Brazil: implications for conservation in a human-dominated landscapeConservation Genecits. v. 12 (6), p. 1.447-55. 2011.

Bits of Mystery DNA, Far From ‘Junk,’ Play Crucial Role (N.Y.Times)

By GINA KOLATA

Published: September 5, 2012

Among the many mysteries of human biology is why complex diseases like diabeteshigh blood pressure and psychiatric disorders are so difficult to predict and, often, to treat. An equally perplexing puzzle is why one individual gets a disease like cancer or depression, while an identical twin remains perfectly healthy.

Béatrice de Géa for The New York Times. “It is like opening a wiring closet and seeing a hairball of wires,” Mark Gerstein of Yale University said of the DNA intricacies.

Now scientists have discovered a vital clue to unraveling these riddles. The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches.

The findings, which are the fruit of an immense federal project involving 440 scientists from 32 laboratories around the world, will have immediate applications for understanding how alterations in the non-gene parts of DNA contribute to human diseases, which may in turn lead to new drugs. They can also help explain how the environment can affect disease risk. In the case of identical twins, small changes in environmental exposure can slightly alter gene switches, with the result that one twin gets a disease and the other does not.

As scientists delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered a complex system that controls genes. At least 80 percent of this DNA is active and needed. The result of the work is an annotated road map of much of this DNA, noting what it is doing and how. It includes the system of switches that, acting like dimmer switches for lights, control which genes are used in a cell and when they are used, and determine, for instance, whether a cell becomes a liver cell or a neuron.

“It’s Google Maps,” said Eric Lander, president of the Broad Institute, a joint research endeavor of Harvard and the Massachusetts Institute of Technology. In contrast, the project’s predecessor, the Human Genome Project, which determined the entire sequence of human DNA, “was like getting a picture of Earth from space,” he said. “It doesn’t tell you where the roads are, it doesn’t tell you what traffic is like at what time of the day, it doesn’t tell you where the good restaurants are, or the hospitals or the cities or the rivers.”

The new result “is a stunning resource,” said Dr. Lander, who was not involved in the research that produced it but was a leader in the Human Genome Project. “My head explodes at the amount of data.”

The discoveries were published on Wednesday in six papers in the journal Nature and in 24 papers in Genome Research and Genome Biology. In addition, The Journal of Biological Chemistry is publishing six review articles, and Science is publishing yet another article.

Human DNA is “a lot more active than we expected, and there are a lot more things happening than we expected,” said Ewan Birney of the European Molecular Biology Laboratory-European Bioinformatics Institute, a lead researcher on the project.

In one of the Nature papers, researchers link the gene switches to a range of human diseases — multiple sclerosislupusrheumatoid arthritisCrohn’s diseaseceliac disease — and even to traits like height. In large studies over the past decade, scientists found that minor changes in human DNA sequences increase the risk that a person will get those diseases. But those changes were in the junk, now often referred to as the dark matter — they were not changes in genes — and their significance was not clear. The new analysis reveals that a great many of those changes alter gene switches and are highly significant.

“Most of the changes that affect disease don’t lie in the genes themselves; they lie in the switches,” said Michael Snyder, a Stanford University researcher for the project, called Encode, for Encyclopedia of DNA Elements.

And that, said Dr. Bradley Bernstein, an Encode researcher at Massachusetts General Hospital, “is a really big deal.” He added, “I don’t think anyone predicted that would be the case.”

The discoveries also can reveal which genetic changes are important in cancer, and why. As they began determining the DNA sequences of cancer cells, researchers realized that most of the thousands of DNA changes in cancer cells were not in genes; they were in the dark matter. The challenge is to figure out which of those changes are driving the cancer’s growth.

“These papers are very significant,” said Dr. Mark A. Rubin, a prostate cancer genomics researcher at Weill Cornell Medical College. Dr. Rubin, who was not part of the Encode project, added, “They will definitely have an impact on our medical research on cancer.”

In prostate cancer, for example, his group found mutations in important genes that are not readily attacked by drugs. But Encode, by showing which regions of the dark matter control those genes, gives another way to attack them: target those controlling switches.

Dr. Rubin, who also used the Google Maps analogy, explained: “Now you can follow the roads and see the traffic circulation. That’s exactly the same way we will use these data in cancer research.” Encode provides a road map with traffic patterns for alternate ways to go after cancer genes, he said.

Dr. Bernstein said, “This is a resource, like the human genome, that will drive science forward.”

The system, though, is stunningly complex, with many redundancies. Just the idea of so many switches was almost incomprehensible, Dr. Bernstein said.

There also is a sort of DNA wiring system that is almost inconceivably intricate.

“It is like opening a wiring closet and seeing a hairball of wires,” said Mark Gerstein, an Encode researcher from Yale. “We tried to unravel this hairball and make it interpretable.”

There is another sort of hairball as well: the complex three-dimensional structure of DNA. Human DNA is such a long strand — about 10 feet of DNA stuffed into a microscopic nucleus of a cell — that it fits only because it is tightly wound and coiled around itself. When they looked at the three-dimensional structure — the hairball — Encode researchers discovered that small segments of dark-matter DNA are often quite close to genes they control. In the past, when they analyzed only the uncoiled length of DNA, those controlling regions appeared to be far from the genes they affect.

The project began in 2003, as researchers began to appreciate how little they knew about human DNA. In recent years, some began to find switches in the 99 percent of human DNA that is not genes, but they could not fully characterize or explain what a vast majority of it was doing.

The thought before the start of the project, said Thomas Gingeras, an Encode researcher from Cold Spring Harbor Laboratory, was that only 5 to 10 percent of the DNA in a human being was actually being used.

The big surprise was not only that almost all of the DNA is used but also that a large proportion of it is gene switches. Before Encode, said Dr. John Stamatoyannopoulos, a University of Washington scientist who was part of the project, “if you had said half of the genome and probably more has instructions for turning genes on and off, I don’t think people would have believed you.”

By the time the National Human Genome Research Institute, part of the National Institutes of Health, embarked on Encode, major advances in DNA sequencing and computational biology had made it conceivable to try to understand the dark matter of human DNA. Even so, the analysis was daunting — the researchers generated 15 trillion bytes of raw data. Analyzing the data required the equivalent of more than 300 years of computer time.

Just organizing the researchers and coordinating the work was a huge undertaking. Dr. Gerstein, one of the project’s leaders, has produced a diagram of the authors with their connections to one another. It looks nearly as complicated as the wiring diagram for the human DNA switches. Now that part of the work is done, and the hundreds of authors have written their papers.

“There is literally a flotilla of papers,” Dr. Gerstein said. But, he added, more work has yet to be done — there are still parts of the genome that have not been figured out.

That, though, is for the next stage of Encode.

*   *   *

Published: September 5, 2012

Rethinking ‘Junk’ DNA

A large group of scientists has found that so-called junk DNA, which makes up most of the human genome, does much more than previously thought.

GENES: Each human cell contains about 10 feet of DNA, coiled into a dense tangle. But only a very small percentage of DNA encodes genes, which control inherited traits like eye color, blood type and so on.

JUNK DNA: Stretches of DNA around and between genes seemed to do nothing, and were called junk DNA. But now researchers think that the junk DNA contains a large number of tiny genetic switches, controlling how genes function within the cell.

REGULATION: The many genetic regulators seem to be arranged in a complex and redundant hierarchy. Scientists are only beginning to map and understand this network, which regulates how cells, organs and tissues behave.

DISEASE: Errors or mutations in genetic switches can disrupt the network and lead to a range of diseases. The new findings will spur further research and may lead to new drugs and treatments.

 

First Holistic View of How Human Genome Actually Works: ENCODE Study Produces Massive Data Set (Science Daily)

ScienceDaily (Sep. 5, 2012) — The Human Genome Project produced an almost complete order of the 3 billion pairs of chemical letters in the DNA that embodies the human genetic code — but little about the way this blueprint works. Now, after a multi-year concerted effort by more than 440 researchers in 32 labs around the world, a more dynamic picture gives the first holistic view of how the human genome actually does its job.

William Noble, professor of genome sciences and computer science, in the data center at the William H. Foege Building. Noble, an expert on machine learning, and his team designed artificial intellience programs to analyze ENCODE data. These computer programs can learn from experience, recognize patterns, and organize information into categories understandable to scientists. The center houses systems for a wide variety of genetic research. The computer center has the capacity to store and analyze a tremendous amount of data, the equivalent of a 670-page autobiography of each person on earth, uncompressed.The computing resources analyze over 4 pentabytes of genomic data a year. (Credit: Clare McLean, Courtesy of University of Washington)

During the new study, researchers linked more than 80 percent of the human genome sequence to a specific biological function and mapped more than 4 million regulatory regions where proteins specifically interact with the DNA. These findings represent a significant advance in understanding the precise and complex controls over the expression of genetic information within a cell. The findings bring into much sharper focus the continually active genome in which proteins routinely turn genes on and off using sites that are sometimes at great distances from the genes themselves. They also identify where chemical modifications of DNA influence gene expression and where various functional forms of RNA, a form of nucleic acid related to DNA, help regulate the whole system.

“During the early debates about the Human Genome Project, researchers had predicted that only a few percent of the human genome sequence encoded proteins, the workhorses of the cell, and that the rest was junk. We now know that this conclusion was wrong,” said Eric D. Green, M.D., Ph.D., director of the National Human Genome Research Institute (NHGRI), a part of the National Institutes of Health. “ENCODE has revealed that most of the human genome is involved in the complex molecular choreography required for converting genetic information into living cells and organisms.”

NHGRI organized the research project producing these results; it is called the Encyclopedia oDNA Elements or ENCODE. Launched in 2003, ENCODE’s goal of identifying all of the genome’s functional elements seemed just as daunting as sequencing that first human genome. ENCODE was launched as a pilot project to develop the methods and strategies needed to produce results and did so by focusing on only 1 percent of the human genome. By 2007, NHGRI concluded that the technology had sufficiently evolved for a full-scale project, in which the institute invested approximately $123 million over five years. In addition, NHGRI devoted about $40 million to the ENCODE pilot project, plus approximately $125 million to ENCODE-related technology development and model organism research since 2003.

The scale of the effort has been remarkable. Hundreds of researchers across the United States, United Kingdom, Spain, Singapore and Japan performed more than 1,600 sets of experiments on 147 types of tissue with technologies standardized across the consortium. The experiments relied on innovative uses of next-generation DNA sequencing technologies, which had only become available around five years ago, due in large part to advances enabled by NHGRI’s DNA sequencing technology development program. In total, ENCODE generated more than 15 trillion bytes of raw data and consumed the equivalent of more than 300 years of computer time to analyze.

“We’ve come a long way,” said Ewan Birney, Ph.D., of the European Bioinformatics Institute, in the United Kingdom, and lead analysis coordinator for the ENCODE project. “By carefully piecing together a simply staggering variety of data, we’ve shown that the human genome is simply alive with switches, turning our genes on and off and controlling when and where proteins are produced. ENCODE has taken our knowledge of the genome to the next level, and all of that knowledge is being shared openly.”

The ENCODE Consortium placed the resulting data sets as soon as they were verified for accuracy, prior to publication, in several databases that can be freely accessed by anyone on the Internet. These data sets can be accessed through the ENCODE project portal (www.encodeproject.org) as well as at the University of California, Santa Cruz genome browser,http://genome.ucsc.edu/ENCODE/, the National Center for Biotechnology Information,http://www.ncbi.nlm.nih.gov/geo/info/ENCODE.html and the European Bioinformatics Institute,http://useast.ensembl.org/Homo_sapiens/encode.html?redirect=mirror;source=www.ensembl.org.

“The ENCODE catalog is like Google Maps for the human genome,” said Elise Feingold, Ph.D., an NHGRI program director who helped start the ENCODE Project. “Simply by selecting the magnification in Google Maps, you can see countries, states, cities, streets, even individual intersections, and by selecting different features, you can get directions, see street names and photos, and get information about traffic and even weather. The ENCODE maps allow researchers to inspect the chromosomes, genes, functional elements and individual nucleotides in the human genome in much the same way.”

The coordinated publication set includes one main integrative paper and five related papers in the journal Nature; 18 papers inGenome Research; and six papers in Genome Biology. The ENCODE data are so complex that the three journals have developed a pioneering way to present the information in an integrated form that they call threads.

“Because ENCODE has generated so much data, we, together with the ENCODE Consortium, have introduced a new way to enable researchers to navigate through the data,” said Magdalena Skipper, Ph.D., senior editor at Nature, which produced the freely available publishing platform on the Internet.

Since the same topics were addressed in different ways in different papers, the new website, www.nature.com/encode, will allow anyone to follow a topic through all of the papers in the ENCODE publication set by clicking on the relevant thread at the Nature ENCODE explorer page. For example, thread number one compiles figures, tables, and text relevant to genetic variation and disease from several papers and displays them all on one page. ENCODE scientists believe this will illuminate many biological themes emerging from the analyses.

In addition to the threaded papers, six review articles are being published in the Journal of Biological Chemistry and two related papers in Science and one in Cell.

The ENCODE data are rapidly becoming a fundamental resource for researchers to help understand human biology and disease. More than 100 papers using ENCODE data have been published by investigators who were not part of the ENCODE Project, but who have used the data in disease research. For example, many regions of the human genome that do not contain protein-coding genes have been associated with disease. Instead, the disease-linked genetic changes appear to occur in vast tracts of sequence between genes where ENCODE has identified many regulatory sites. Further study will be needed to understand how specific variants in these genomic areas contribute to disease.

“We were surprised that disease-linked genetic variants are not in protein-coding regions,” said Mike Pazin, Ph.D., an NHGRI program director working on ENCODE. “We expect to find that many genetic changes causing a disorder are within regulatory regions, or switches, that affect how much protein is produced or when the protein is produced, rather than affecting the structure of the protein itself. The medical condition will occur because the gene is aberrantly turned on or turned off or abnormal amounts of the protein are made. Far from being junk DNA, this regulatory DNA clearly makes important contributions to human health and disease.”

Identifying regulatory regions will also help researchers explain why different types of cells have different properties. For example why do muscle cells generate force while liver cells break down food? Scientists know that muscle cells turn on some genes that only work in muscle, but it has not been previously possible to examine the regulatory elements that control that process. ENCODE has laid a foundation for these kinds of studies by examining more than 140 of the hundreds of cell types found in the human body and identifying many of the cell type-specific control elements.

Despite the enormity of the dataset described in this historic collection of publications, it does not comprehensively describe all of the functional genomic elements in all of the different types of cells in the human body. NHGRI plans to invest in additional ENCODE-related research for at least another four years. During the next phase, ENCODE will increase the depth of the catalog with respect to the types of functional elements and cell types studied. It will also develop new tools for more sophisticated analyses of the data.

Journal References:

  1. Magdalena Skipper, Ritu Dhand, Philip Campbell.Presenting ENCODENature, 2012; 489 (7414): 45 DOI:10.1038/489045a
  2. Joseph R. Ecker, Wendy A. Bickmore, Inês Barroso, Jonathan K. Pritchard, Yoav Gilad, Eran Segal. Genomics: ENCODE explainedNature, 2012; 489 (7414): 52 DOI:10.1038/489052a
  3. The ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome.Nature, 2012; 489 (7414): 57 DOI: 10.1038/nature11247

The eyes have it: Men do see things differently to women (BioMed Central)

By Hilary Glover

BioMed Central

The way that the visual centers of men and women’s brains works is different, finds new research published in BioMed Central’s open access journal Biology of Sex Differences. Men have greater sensitivity to fine detail and rapidly moving stimuli, but women are better at discriminating between colors.

In the brain there are high concentrations of male sex hormone (androgen) receptors throughout cerebral cortex, especially in the visual cortex which is responsible for processing images. Androgens are also responsible for controlling the development of neurons in the visual cortex during embryogenesis, meaning that males have 25% more of these neurons than females.

Researchers from Brooklyn and Hunter Colleges of the City University of New York compared the vision of men and women aged over 16 from both college and high school, including students and staff. All volunteers were required to have normal color vision and 20/20 sight (or 20/20 when corrected by glasses or contact lenses).

When the volunteers were required to describe colors shown to them across the visual spectrum it became obvious that the color vision of men was shifted, and that they required a slightly longer wavelength to experience the same hue as the women. The males also had a broader range in the center of the spectrum where they were less able to discriminate between colors.

An image of light and dark bars was used to measure contrast-sensitivity functions (CSF) of vision; the bars were either horizontal or vertical and volunteers had to choose which one they saw. In each image, when the light and dark bars were alternated the image appeared to flicker.

By varying how rapidly the bars alternated or how close together they were, the team found that at moderate rates of image change, observers lost sensitivity for close together bars, and gained sensitivity when the bars were farther apart. However when the image change was faster both sexes were less able to resolve the images over all bar widths. Overall the men were better able to resolve more rapidly changing images that were closer together than the women.

Prof Israel Abramov, who led this study commented, “As with other senses, such as hearing and the olfactory system, there are marked sex differences in vision between men and women. The elements of vision we measured are determined by inputs from specific sets of thalamic neurons into the primary visual cortex. We suggest that, since these neurons are guided by the cortex during embryogenesis, that testosterone plays a major role, somehow leading to different connectivity between males and females. The evolutionary driving force between these differences is less clear.”

Sources

Sex & vision I: Spatio-temporal resolution Israel Abramov, James Gordon, Olga Feldman and Alla Chavarga Biology of Sex Differences (in press)

Sex and vision II: Color appearance of monochromatic lights Israel Abramov, James Gordon, Olga Feldman and Alla Chavarga Biology of Sex Differences (in press)

New DNA Analysis Shows Ancient Humans Interbred with Denisovans (Scientific American)

A new high-coverage DNA sequencing method reconstructs the full genome of Denisovans–relatives to both Neandertals and humans–from genetic fragments in a single finger bone

By Katherine Harmon  | Thursday, August 30, 2012

denisovan genome finger boneFRAGMENT OF A FINGER: This replica of the Denisovan finger bone shows just how small of a sample the researchers had to extract DNA from.Image: Image courtesy of Max Planck Institute for Evolutionary Anthropology

Tens of thousands of years ago modern humans crossed paths with the group of hominins known as the Neandertals. Researchers now think they also met another, less-known group called the Denisovans. The only trace that we have found, however, is a single finger bone and two teeth, but those fragments have been enough to cradle wisps of Denisovan DNA across thousands of years inside a Siberian cave. Now a team of scientists has been able to reconstruct their entire genome from these meager fragments. The analysis adds new twists to prevailing notions about archaic human history.

“Denisova is a big surprise,” says John Hawks, a biological anthropologist at the University of Wisconsin–Madison who was not involved in the new research. On its own, a simple finger bone in a cave would have been assumed to belong to a human, Neandertal or other hominin. But when researchers first sequenced a small section of DNA in 2010—a section that covered about 1.9 percent of the genome—they were able to tell that the specimen was neither. “It was the first time a new group of distinct humans was discovered” via genetic analysis rather than by anatomical description, said Svante Pääbo, a researcher at the Max Planck Institute (M.P.I.) for Evolutionary Anthropology in Germany, in a conference call with reporters.

Now Pääbo and his colleagues have devised a new method of genetic analysis that allowed them to reconstruct the entire Denisovan genome with nearly all of the genome sequenced approximately 30 times over akin to what we can do for modern humans. Within this genome, researchers have found clues into not only this group of mysterious hominins, but also our own evolutionary past. Denisovans appear to have been more closely related to Neandertals than to humans, but the evidence also suggests that Denisovans and humans interbred. The new analysis also suggests new ways that early humans may have spread across the globe. The findings were published online August 30 in Science.

Who were the Denisovans?
Unfortunately, the Denisovan genome doesn’t provide many more clues about what this hominin looked like than a pinky bone does. The researchers will only conclude that Denisovans likely had dark skin. They also note that there are alleles “consistent” with those known to call for brown hair and brown eyes. Other than that, they cannot say.

Yet the new genetic analysis does support the hypothesis that Neandertals and Denisovans were more closely related to one another than either was to modern humans. The analysis suggests that the modern human line diverged from what would become the Denisovan line as long as 700,000 years ago—but possibly as recently as 170,000 years ago.

Denisovans also interbred with ancient modern humans, according to Pääbo and his team. Even though the sole fossil specimen was found in the mountains of Siberia, contemporary humans from Melanesia (a region in the South Pacific) seem to be the most likely to harbor Denisovan DNA. The researchers estimate that some 6 percent of contemporary Papuans’ genomes come from Denisovans. Australian aborigines and those from Southeast Asian islands also have traces of Denisovan DNA. This suggests that the two groups might have crossed paths in central Asia and then the modern humans continued on to colonize the islands of Oceania.

Yet contemporary residents of mainland Asia do not seem to posses Denisovian traces in their DNA, a “very curious” fact, Hawks says. “We’re looking at a very interesting population scenario”—one that does not jibe entirely with what we thought we knew about how waves modern human populations migrated into and through Asia and out to Oceania’s islands. This new genetic evidence might indicate that perhaps an early wave of humans moved through Asia, mixed with Denisovans and then relocated to the islands—to be replaced in Asia by later waves of human migrants from Africa. “It’s not totally obvious that that works really well with what we know about the diversity of Asians and Australians,” Hawks says. But further genetic analysis and study should help to clarify these early migrations.

Just as with modern Homo sapiens, the genome of a single individual cannot tell us exactly what genes and traits are specific to all Denisovans. Yet, just one genome can reveal the genetic diversity of an entire population. Each of our genomes contains information about generations far beyond those of our parents and grandparents, said David Reich, a researcher at the Massachusetts Institute of Technology–Harvard University Broad Institute and a co-author on the paper. Scientists can compare and contrast the set of genes on each chromosome—passed down from each parent—and extrapolate this process back through the generations. “You contain a multitude of ancestors within you,” Reich said, borrowing from Walt Whitman.

The new research reveals that the Denisovans had low genetic diversity—just 26 to 33 percent of the genetic diversity of contemporary European or Asian populations. And for the Denisovans, the population on the whole seems to have been very small for hundreds of thousands of years, with relatively little genetic diversity throughout their history.

Curiously, the researchers noted in their paper, the Denisovan population shows “a drastic decline in size at the time when the modern human population began to expand.”

Why were modern humans so successful whereas Denisovans (and Neandertals) went extinct? Pääbo and his co-authors could not resist looking into the genetic factors that might be at work. Some of the key differences, they note, center around brain development and synaptic connectivity. “It makes sense that what pops up is connectivity in the brain,” Pääbo noted. Neandertals had a similar brain size–to-body ratio as we do, so rather than cranial capacity, it might have been underlying neurological differences that could explain why we flourished while they died out, he said.

Hawks counters that it might be a little early to begin drawing conclusions about human brain evolution from genetic comparisons with archaic relatives. Decoding the genetic map of the brain and cognition from a genome is still a long way off, he notes—unraveling skin color is still difficult enough given our current technologies and knowledge.

New sequencing for old DNA
The Denisovan results rely on a new method of genetic analysis developed by paper co-author Matthias Meyer, also of M.P.I. The procedure allows the researchers to sequence the full genome by using single strands of genetic material rather than the typical double strands required. The technique, which they are calling a single-stranded library preparation, involves stripping the genetic material down to individual strands to copy and avoids a purification step, which can lose precious genetic material.

The finger bone—just one disklike phalanx—is so small that it does not contain enough usable carbon for dating, the researchers note. But by counting the number of genetic mutations in a genome and comparing them with other living relatives, such as modern humans and chimpanzees, given assumed rates of mutations since breaking with a last common ancestor, “for the first time you can try to estimate this number into a date and provide molecular dating of the fossil,” Meyer said. With the new resolution, the researchers estimate the age of the bone to 74,000 to 82,000 years ago. But that is a wide window, and previous archaeological estimates for the bone are a bit younger, ranging from 30,000 to 50,000 years old. These genetic estimations are also still in limbo because of ongoing debate about the average rate of genetic mutations over time, which could skew the age. “Nevertheless,” the researchers noted in their paper, “the results suggest that in the future it will be possible to determine dates of fossils based on genome sequences.”

This new sequencing approach can be used for any DNA that is too fragmented to be read well through more traditional methods. Meyer noted that it could come in handy for analysis of both ancient DNA and contemporary forensic evidence, which also often contains only fragments of genetic material.

Hawks is excited about the new sequencing technology. It is also helpful to have a technology developed specifically for the evolutionary field, he notes. “We’re always using the new techniques from other fields, and this is a case where the new technique is developed just for this.”

Hawks himself has heard from the researchers that have worked with the Denisovan samples that “the Denisovan pinky is just extraordinary” in terms of the amount of DNA preserved in it. Most bone fragments would be expected to contain less than 5 percent of the individual’s endogenous DNA, but this fortuitous finger had a surprising 70 percent, the researchers noted in the study. And many Neandertal fragments have been preserved in vastly different states—many are far worse off than this Denisovan finger bone.

The new sequencing approach could also improve our understanding of known specimens and the evolutionary landscape as a whole. “It’s going to increase the yield from other fossils,” Hawks notes. Many of the Neandertal specimens, for example, have only a small fraction of their genome sequenced. “If we can go from 2 percent to the whole genome, that opens up a lot more,” Hawks says. “Going back further in time will be exciting,” he notes, and this new technique should allow us to do that. “There’s a huge race on—it’s exciting.”

The Denisovans might be the first non-Neandertal archaic human to be sequenced, but they are likely not going to be the last. The researchers behind this new study are already at work using the new single-strand sequencing technique to reexamine older specimens. (Meyer said they were working on reassessing old samples but would not specify which specimens they were studying—the mysterious “hobbit” H. floresiensis would be a worthy candidate.) Pääbo suggests Asia as a particularly promising location to look for other Denisovan-like groups. “I would be surprised if there were not other groups to be found there in the future,” he said.

Taking this technique to specimens from Africa is also likely to yield some exciting results, Hawks says. Africa, with its rich human evolutionary history, holds the greatest genetic diversity. The genomes of contemporary pygmy and hunter–gatherer tribes in Africa, for example, have roughly as many differences as do those of European modern humans and Neandertals. So “any ancient specimen that we find in Africa might be as different from us as Neandertals,” Hawks says. “Anything we find from the right place might be another Denisovan.”

Gene That Predicts Happiness in Women Discovered (Science Daily)

ScienceDaily (Aug. 28, 2012) — A new study has found a gene that appears to make women happy, but it doesn’t work for men. The finding may help explain why women are often happier than men, the research team said.

A new study has found a gene that appears to make women happy, but it doesn’t work for men. The finding may help explain why women are often happier than men. (Credit: © Yuri Arcurs / Fotolia)

Scientists at the University of South Florida (USF), the National Institutes of Health (NIH), Columbia University and the New York State Psychiatric Institute reported that the low-expression form of the gene monoamine oxidase A (MAOA) is associated with higher self-reported happiness in women. No such association was found in men.

The findings appear online in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry.

“This is the first happiness gene for women,” said lead author Henian Chen, MD, PhD, associate professor in the Department of Epidemiology and Biostatistics, USF College of Public Health.

“I was surprised by the result, because low expression of MAOA has been related to some negative outcomes like alcoholism, aggressiveness and antisocial behavior,” said Chen, who directs the Biostatistics Core at the USF Health Morsani College of Medicine’s Clinical and Translational Sciences Institute. “It’s even called the warrior gene by some scientists, but, at least for women, our study points to a brighter side of this gene.”

While they experience higher rates of mood and anxiety disorders, women tend to report greater overall life happiness than do men. The reason for this remains unclear, Chen said. “This new finding may help us to explain the gender difference and provide more insight into the link between specific genes and human happiness.”

The MAOA gene regulates the activity of an enzyme that breaks down serontin, dopamine and other neurotransmitters in the brain — the same “feel-good” chemicals targeted by many antidepressants. The low-expression version of the MAOA gene promotes higher levels of monoamine, which allows larger amounts of these neurotransmitters to stay in the brain and boost mood.

The researchers analyzed data from a population-based sample of 345 individuals — 193 women and 152 men — participating in Children in the Community, a longitudinal mental health study. The DNA of study subjects had been analyzed for MAOA gene variation and their self-reported happiness was scored by a widely used and validated scale.

After controlling for various factors, ranging from age and education to income, the researchers found that women with the low-expression type of MAOA were significantly happier than others. Compared to women with no copies of the low-expression version of the MAOA gene, women with one copy scored higher on the happiness scale and those with two copies increased their score even more.

While a substantial number of men carried a copy of the “happy” version of the MAOA gene, they reported no more happiness than those without it.

So, why the genetic gender gap in feeling good?

The researchers suspect the difference may be explained in part by the hormone testosterone, found in much smaller amounts in women than in men. Chen and his co-authors suggest that testosterone may cancel out the positive effect of MAOA on happiness in men.

The potential benefit of MAOA in boys could wane as testosterone levels rise with puberty, Chen said. “Maybe men are happier before adolescence because their testosterone levels are lower.”

Chen emphasizes that more research is needed to identify which specific genes influence resilience and subjective well-being, especially since studies of twins estimate genetic factors account for 35 to 50 percent of the variance in human happiness.

While happiness is not determined by a single gene, there is likely a set of genes that, along with life experiences, shape our individual happiness levels, Chen said. “I think the time is right for more genetic studies that focus on well-being and happiness.”

“Certainly it could be argued that how well-being is enhanced deserves at least as much attention as how (mental) disorders arise; however, such knowledge remains limited.”

The study by Chen and colleagues was supported by the National Institutes of Health and a USF proposal enhancement grant.

Journal Reference:

  1. Henian Chen, Daniel S. Pine, Monique Ernst, Elena Gorodetsky, Stephanie Kasen, Kathy Gordon, David Goldman, Patricia Cohen. The MAOA gene predicts happiness in womenProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2012; DOI:10.1016/j.pnpbp.2012.07.018

The Role of Genes in Political Behavior (Science Daily)

ScienceDaily (Aug. 27, 2012) — Politics and genetics have traditionally been considered non-overlapping fields, but over the past decade it has become clear that genes can influence political behavior, according to a review published online August 27th in Trends in Genetics. This paradigm shift has led to novel insights into why people vary in their political preferences and could have important implications for public policy.

“We’re seeing an awakening in the social sciences, and the wall that divided politics and genetics is really starting to fall apart,” says review author Peter Hatemi of the University of Sydney. “This is a big advance, because the two fields could inform each other to answer some very complex questions about individual differences in political views.”

In the past, social scientists had assumed that political preferences were shaped by social learning and environmental factors, but recent studies suggest that genes also strongly influence political traits. Twin studies show that genes have some influence on why people differ on political issues such as the death penalty, unemployment and abortion. Because this field of research is relatively new, only a handful of genes have been implicated in political ideology and partisanship, voter turnout, and political violence.

Future research, including gene-expression and sequencing studies, may lead to deeper insights into genetic influences on political views and have a greater impact on public policy. “Making the public aware of how their mind works and affects their political behavior is critically important,” Hatemi says. “This has real implications for the reduction of discrimination, foreign policy, public health, attitude change and many other political issues.”

Journal Reference:

  1. Peter K Hatemi and Rose McDermott. The Genetics of Politics: Discovery, Challenges and ProgressTrends in Genetics, August 27, 2012 DOI: 10.1016/j.tig.2012.07.004

Pai de gêmeos, um negro e outro branco (Extra)

Bruno Cunha

Fonte Extra

Finalmente eles foram reconhecidos no futebol. Enquanto um é zagueiro, tem cabelos crespos e adora doce, o outro é atacante, tem fios louros e prefere salgado. Com as diferenças, ficava difícil perceber que David Evangelista de Oliveira, o branco, e Nícolas, o negro, são irmãos gêmeos.

— Os pais dos coleguinhas do futebol achavam que só um era meu filho e que o outro era um amiguinho dele. E olha que os dois já treinam há um ano e meio. Mas só agora descobriram que são irmãos gêmeos — conta o montador de peças de laboratório Luis Carlos de Oliveira Silva, de 42 anos, pai das crianças.

Fama no bairro

Morador de Campo Grande, Luis tomou um susto quando soube da dupla gravidez da mulher, Audicelia Evangelista, de 45 anos. E outro após o nascimento dos filhos, um negro, como o pai, e outro branco, como a mãe.

— Na época, os colegas brincavam: “ah, esse aí não é seu filho, não!”. Uma vez entrei numa maternidade e o David me chamou de pai. O segurança cochichou: “não é filho dele.” Mas eu penso: os dois puxaram ao pai e à mãe — afirma Luis.

Na porta do quarto, a frase “gêmeos em ação”
Na porta do quarto, a frase “gêmeos em ação” Foto: Nina Lima / Extra

Famosos no sub-bairro Santa Rosa, Nícolas e David, aos 9 anos, já começam a colher os frutos da fama que os levou a um programa de TV ainda recém-nascidos. Outro dia mesmo foram seguidos por duas meninas que descobriram onde moravam.

— Cheguei do trabalho umas 19h30m e peguei o Nícolas passando gel no cabelo e o Davi se arrumando. Logo em seguida, duas meninas gritaram o nome deles aqui no portão. Elas estavam tomando coragem para chamá-los para sair — explica o pai, que se diverte ao saber que os filhos já estão se interessando pelas meninas.

Os gêmeos
Os gêmeos Foto: Acervo pessoal / Divulgação

Estimativa: menos de 1% de chance de incidência

O nascimento de irmãos gêmeos, um negro e outro branco, ainda surpreende. Em 2006, por exemplo, o EXTRA mostrou o caso dos irmãos Pedro e Nathan Henrique Rodrigues, que intrigou Costa Barros.

Um ano depois, o cabeleireiro Carlos Henrique Fonseca, o pai, na época com 26 anos, contou que muitas pessoas ainda estranhavam quando viam Pedro, negro como ele, ao lado de Nathan, branco como mãe, a então frentista Valéria Gomes, de 22 anos.

Diferentes, mas torcem pelo mesmo time
Diferentes, mas torcem pelo mesmo time Foto: Nina Lima / Extra

Miscigenação

A cegonha também foi generosa, em Botafogo, onde vivem as gêmeas Beatriz e Maria Gaia Gerstner, hoje com 8 anos. Uma é morena como a mãe e a outra é branca como o pai, um alemão.

— Quando estou com a branca não acham que é minha filha. E quando o pai está com a morena é a mesma coisa — conta a mãe, Janaína Gaia, de 35 anos, hoje separada do pai delas.

A diretora do Centro Vida — Reprodução Humana Assistida, na Barra, na Zona Oeste, Maria Cecília Erthal, estima que há menos de 1% de chance do nascimento de gêmeos diferentes.

— É a miscigenação que faz com que os genes de pais negros e brancos se encontrem — explica.

*   *   *

Jemima Pompeu enviou o seguinte comentário:

Gêmeos com cores de pele diferentes surpreendem pais, mas não os cientistas. Veja alguns casos no link abaixo:

Nature or nurture? It may depend on where you live (AAAS)

12-Jun-2012

By Craig Brierley

The extent to which our development is affected by nature or nurture – our genetic make-up or our environment – may differ depending on where we live, according to research funded by the Medical Research Council and the Wellcome Trust.

In a study published today in the journal Molecular Psychiatry, researchers from the Twins Early Development Study at King’s College London’s Institute of Psychiatry studied data from over 6,700 families relating to 45 childhood characteristics, from IQ and hyperactivity through to height and weight. They found that genetic and environmental contributions to these characteristics vary geographically in the United Kingdom, and published their results online as a series of nature-nurture maps.

Our development, health and behaviour are determined by complex interactions between our genetic make-up and the environment in which we live. For example, we may carry genes that increase our risk of developing type 2 diabetes, but if we eat a healthy diet and get sufficient exercise, we may not develop the disease. Similarly, someone may carry genes that reduce his or her risk of developing lung cancer, but heavy smoking may still lead to the disease.

The UK-based Twins Early Development Study follows over 13,000 pairs of twins, both identical and non-identical, born between 1994 and 1996. When the twins were age 12, the researchers carried out a broad survey to assess a wide range of cognitive abilities, behavioural (and other) traits, environments and academic achievement in 6,759 twin pairs. The researchers then designed an analysis that reveals the UK’s genetic and environmental hotspots, something which had never been done before.

“These days we’re used to the idea that it’s not a question of nature or nurture; everything, including our behaviour, is a little of both,” explains Dr Oliver Davis, a Sir Henry Wellcome Postdoctoral Fellow at King’s College London’s Institute of Psychiatry. “But when we saw the maps, the first thing that struck us was how much the balance of genes and environments can vary from region to region.”

“Take a trait like classroom behaviour problems. From our maps we can tell that in most of the UK around 60% of the difference between people is explained by genes. However, in the South East genes aren’t as important: they explain less than half of the variation. For classroom behaviour, London is an ‘environmental hotspot’.”

The maps give the researchers a global overview of how the environment interacts with our genomes, without homing in on particular genes or environments. However, the patterns have given them important clues about which environments to explore in more detail.

“The nature-nurture maps help us to spot patterns in the complex data, and to try to work out what’s causing these patterns,” says Dr Davis. “For our classroom behaviour example, we realised that one thing that varies more in London is household income. When we compare maps of income inequality to our nature-nurture map for classroom behaviour, we find income inequality may account for some of the pattern.

“Of course, this is just one example. There are any number of environments that vary geographically in the UK, from social environments like health care or education provision to physical environments like altitude, the weather or pollution. Our approach is all about tracking down those environments that you wouldn’t necessarily think of at first.”

It may be relatively easy to explain environmental hotspots, but what about the genetic hotspots that appear on the maps: do people’s genomes vary more in those regions? The researchers believe this is not the case; rather, genetic hotspots are areas where the environment exposes the effects of genetic variation.

For example, researchers searching for gene variants that increase the risk of hay fever may study populations from two regions. In the first region people live among fields of wind-pollinated crops, whereas the second region is miles away from those fields. In this second region, where no one is exposed to pollen, no one develops hay fever; hence any genetic differences between people living in this region would be invisible.

On the other hand, in the first region, where people live among the fields of crops, they will all be exposed to pollen and differences between the people with a genetic susceptibility to hay fever and the people without will stand out. That would make the region a genetic hotspot for hay fever.

“The message that these maps really drive home is that your genes aren’t your destiny. There are plenty of things that can affect how your particular human genome expresses itself, and one of those things is where you grow up,” says Dr Davis.

Hope, Hype and Genetic Breakthroughs (Wall Street Journal)

By CARL ZIMMER

I talk to scientists for a living, and one of my most memorable conversations took place a couple of years ago with an engineer who put electrodes in bird brains. The electrodes were implanted into the song-generating region of the brain, and he could control them with a wireless remote. When he pressed a button, a bird singing in a cage across the lab would fall silent. Press again, and it would resume its song.

I could instantly see a future in which this technology brought happiness to millions of people. Imagine a girl blind from birth. You could implant a future version of these wireless electrodes in the back of her brain and then feed it images from a video camera.

As a journalist, I tried to get the engineer to explore what seemed to me to be the inevitable benefits of his research. To his great credit, he wouldn’t. He wasn’t even sure his design would ever see the inside of a human skull. There were just too many ways for it to go wrong. He wanted to be very sure that I understood that and that I wouldn’t claim otherwise. “False hope,” he warned me, “is a sinful thing.”

EPEGINE1

Stephen Voss. Gene therapy allowed this once-blind dog to see again.

Over the past two centuries, medical research has yielded some awesome treatments: smallpox wiped out with vaccines, deadly bacteria thwarted by antibiotics, face transplants. But when we look back across history, we forget the many years of failure and struggle behind each of these advances.

This foreshortened view distorts our expectations for research taking place today. We want to believe that every successful experiment means that another grand victory is weeks away. Big stories appear in the press about the next big thing. And then, as the years pass, the next big thing often fails to materialize. We are left with false hope, and the next big thing gets a reputation as the next big lie.

In 1995, a business analyst named Jackie Fenn captured this intellectual whiplash in a simple graph. Again and again, she had seen new advances burst on the scene and generate ridiculous excitement. Eventually they would reach what she dubbed the Peak of Inflated Expectations. Unable to satisfy their promise fast enough, many of them plunged into the Trough of Disillusionment. Their fall didn’t necessarily mean that these technologies were failures. The successful ones slowly emerged again and climbed the Slope of Enlightenment.

When Ms. Fenn drew the Hype Cycle, she had in mind dot-com-bubble technologies like cellphones and broadband. Yet it’s a good model for medical advances too. I could point to many examples of the medical hype cycle, but it’s hard to think of a better one than the subject of Ricki Lewis’s well-researched new book, “The Forever Fix”: gene therapy.

The concept of gene therapy is beguilingly simple. Many devastating disorders are the result of mutant genes. The disease phenylketonuria, for example, is caused by a mutation to a gene involved in breaking down a molecule called phenylalanine. The phenylalanine builds up in the bloodstream, causing brain damage. One solution is to eat a low-phenylalanine diet for your entire life. A much more appealing alternative would be to somehow fix the broken gene, restoring a person’s metabolism to normal.

In “The Forever Fix,” Ms. Lewis chronicles gene therapy’s climb toward the Peak of Inflated Expectations over the course of the 1990s. A geneticist and the author of a widely used textbook, she demonstrates a mastery of the history, even if her narrative sometimes meanders and becomes burdened by clichés. She explains how scientists learned how to identify the particular genes behind genetic disorders. They figured out how to load genes into viruses and then to use those viruses to insert the genes into human cells.

EPEGINE2

Stephen Voss. Alisha Bacoccini is tested on her ability to read letters, at UPenn Hospital, in Philadelphia, PA on Monday, June 23, 2008. Bacoccini is undergoing an experimental gene therapy trial to improve her sight.

By 1999, scientists had enjoyed some promising successes treating people—removing white blood cells from leukemia patients, for example, inserting working genes, and then returning the cells to their bodies. Gene therapy seemed as if it was on the verge of becoming standard medical practice. “Within the next decade, there will be an exponential increase in the use of gene therapy,” Helen M. Blau, the then-director of the gene-therapy technology program at Stanford University, told Business Week.

Within a few weeks of Ms. Blau’s promise, however, gene therapy started falling straight into the Trough. An 18-year-old man named Jesse Gelsinger who suffered from a metabolic disorder had enrolled in a gene-therapy trial. University of Pennsylvania scientists loaded a virus with a working version of an enzyme he needed and injected it into his body. The virus triggered an overwhelming reaction from his immune system and within four days Gelsinger was dead.

Gene therapy nearly came to a halt after his death. An investigation revealed errors and oversights in the design of Gelsinger’s trial. The breathless articles disappeared. Fortunately, research did not stop altogether. Scientists developed new ways of delivering genes without triggering fatal side effects. And they directed their efforts at one part of the body in particular: the eye. The eye is so delicate that inflammation could destroy it. As a result, it has evolved physical barriers that keep the body’s regular immune cells out, as well as a separate battalion of immune cells that are more cautious in their handling of infection.

It occurred to a number of gene-therapy researchers that they could try to treat genetic vision disorders with a very low risk of triggering horrendous side effects of the sort that had claimed Gelsinger’s life. If they injected genes into the eye, they would be unlikely to produce a devastating immune reaction, and any harmful effects would not be able to spread to the rest of the body.

Their hunch paid off. In 2009 scientists reported their first success with gene therapy for a congenital disorder. They treated a rare form of blindness known as Leber’s congenital amaurosis. Children who were once blind can now see.

As “The Forever Fix” shows, gene therapy is now starting its climb up the Slope of Enlightenment. Hundreds of clinical trials are under way to see if gene therapy can treat other diseases, both in and beyond the eye. It still costs a million dollars a patient, but that cost is likely to fall. It’s not yet clear how many other diseases gene therapy will help or how much it will help them, but it is clearly not a false hope.

Gene therapy produced so much excitement because it appealed to the popular idea that genes are software for our bodies. The metaphor only goes so far, though. DNA does not float in isolation. It is intricately wound around spool-like proteins called histones. It is studded with caps made of carbon, hydrogen and oxygen atoms, known as methyl groups. This coiling and capping of DNA allows individual genes to be turned on and off during our lifetimes.

The study of this extra layer of control on our genes is known as epigenetics. In “The Epigenetics Revolution,” molecular biologist Nessa Carey offers an enlightening introduction to what scientists have learned in the past decade about those caps and coils. While she delves into a fair amount of biological detail, she writes clearly and compellingly. As Ms. Carey explains, we depend for our very existence as functioning humans on epigenetics. We begin life as blobs of undifferentiated cells, but epigenetic changes allow some cells to become neurons, others muscle cells and so on.

Epigenetics also plays an important role in many diseases. In cancer cells, genes that are normally only active in embryos can reawaken after decades of slumber. A number of brain disorders, such as autism and schizophrenia, appear to involve the faulty epigenetic programming of genes in neurons.

Scientists got their first inklings about epigenetics decades ago, but in the past few years the field has become hot. In 2008 the National Institutes of Health pledged $190 million to map the epigenetic “marks” on the human genome. New biotech start-ups are trying to carry epigenetic discoveries into the doctor’s office. The FDA has approved cancer drugs that alter the pattern of caps on tumor-cell DNA. Some studies on mice hint that it may be possible to treat depression by taking a pill that adjusts the coils of DNA in neurons.

People seem to be getting giddy about the power of epigenetics in the same way they got giddy about gene therapy in the 1990s. No longer is our destiny written in our DNA: It can be completely overwritten with epigenetics. The excitement is moving far ahead of what the science warrants—or can ever deliver. Last June, an article on the Huffington Post eagerly seized on epigenetics, woefully mangling two biological facts: one, that experiences can alter the epigenetic patterns in the brain; and two, that sometimes epigenetic patterns can be passed down from parents to offspring. The article made a ridiculous leap to claim that we can use meditation to change our own brains and the brains of our children—and thereby alter the course of evolution: “We can jump-start evolution and leverage it on our own terms. We can literally rewire our brains toward greater compassion and cooperation.” You couldn’t ask for a better sign that epigenetics is climbing the Peak of Inflated Expectations at top speed.

The title “The Epigenetics Revolution” unfortunately adds to this unmoored excitement, but in Ms. Carey’s defense, the book itself is careful and measured. Still, epigenetics will probably be plunging soon into the Trough of Disillusionment. It will take years to see whether we can really improve our health with epigenetics or whether this hope will prove to be a false one.

The Forever Fix

By Ricki LewisSt. Martin’s, 323 pages, $25.99

The Epigenetics Revolution

By Nessa CareyColumbia, 339 pages, $26.95

—Mr. Zimmer’s books include “A Planet of Viruses and Evolution: Making Sense of Life,” co-authored with Doug Emlen, to be published in July.

Risco é coisa séria (JC)

JC e-mail 4364, de 14 de Outubro de 2011.

Artigo de Francisco G. Nóbrega enviado ao JC Email pelo autor.

A sociedade moderna está banhada em comunicação. Como “boa notícia não é notícia”, a lente psicológica humana registra sempre um cenário pior que a realidade. A percepção usual é que os riscos de todos os tipos aumentam dia a dia. A redução global da violência, por exemplo, é tema do livro recente do psicólogo da Universidade Harvard, Steven Pinker (http://www.samharris.org/blog/item/qa-with-steven-pinker). Ao arrepio do senso comum, ele demonstra, objetivamente, que estamos progredindo neste quesito.

Mas nossa mente não descança em sua aguda capacidade de detectar outras fontes de risco. Temos alguns campeões de audiência: energia nuclear para eletricidade, alimentos geneticamente modificados e aquecimento global catastrófico e antropogênico. O dano potencial das três ameaças mencionadas, objetivamente, não se concretizou de maneira alguma, embora a terceira ameaça deva se realizar no futuro, segundo seus defensores. As pessoas se encantam com o automóvel e seus acessórios, cada vez mais atraentes. Não se pensa em baní-lo, apesar de resultar em cerca de 40.000 mortos e inúmeros incapacitados cada ano, só no Brasil. David Ropeik, que pertence ao Centro Harvard para Análise de Risco, explica como facilmente se distorce o perigo real de situações. Quanto mais afastadas do senso comum (como radiação e plantas geneticamente modificadas), mais facilmente são manipuladas, por ignorância ou interesses outros, apavorando o cidadão comum. Ropeik explica como este medo sem sentido passa a ser um fator de estresse e um risco objetivo para a saúde das pessoas, devendo ser evitado.

Dentro desse universo, são justificadas as preocupações do Dr. Ferraz (“O feijão nosso de cada dia”, Jornal da Ciência, 6/10/2011). Ele é membro da CTNBio, atua na setorial vegetal/ambiental e sua área de concentração é em agroecologia, o que explica, pelo menos em parte, suas dúvidas. No entanto essas preocupações não têm a consistência sugerida pelo autor e a análise da CTNBio, que resultou na aprovação deste feijão, é confiável.

A comissão se pauta sempre pelas diretivas da legislação que são amplas, para dar conta de todas as possibilidades de risco para os consumidores e meio ambiente. No entanto o corpo técnico existe exatamente para atuar de maneira seletiva e consciente, examinando caso a caso. Os testes são examinadas com o rigor que a modificação introduzida na planta exige para plena segurança. Se as modificações são consideradas sem qualquer risco significativo, os testes são avaliados à luz deste fato.

Testes com muitos animais, altamente confiáveis estatisticamente, seriam exigidos pela comissão na eventualidade de uma planta transgênica produzir, por exemplo, uma molécula pesticida não protéica que seria em tudo semelhante a uma droga produzida pela indústria farmacêutica. Isto poderá acontecer em certo momento, já que as plantas têm capacidade de produzir os mais variados pesticidas naturais para se defenderem na natureza. A substância seria absorvida no intestino e se disseminaria por órgãos e tecidos, possivelmente exercendo efeitos sistêmicos e localizados que exigem avaliação. Isso já aconteceu, sem querer, com uma batata produzida por melhoramento convencional nos EUA. Seu consumo levou a mal estar e foi recolhida apressadamente: portava altos níveis de glicoalcalóides tóxicos para o homem, o que explicava sua excelente resistência às pragas da cultura.

No caso do feijão Embrapa, nenhuma molécula não protéica nova é produzida e o pequeno RNA que interfere com a replicação do vírus, caso alguém venha a ingerir folhas e caules, será um entre centenas ou milhares de RNAs que ingerimos diariamente com qualquer produto vegetal. O RNA introduzido, no entanto, não foi detectado no grão do feijão cozido, usando técnicas extremamente poderosas.

As variações detectadas, se estatisticamente significativas (concentração de vitamina B2 ou cisteína por exemplo) não representam risco algum. A técnica clássica de cultura de tecidos, usada para gerar variedades de qualidade em horticultura e propagação de árvores, reconhecidamente resulta em variações naturais que introduzem certas modificações desejáveis e algumas indesejáveis, que o melhorista depois seleciona. É a variação somaclonal, que também afeta os clones geneticamente modificados na sua fase de seleção.

Portanto, é no mínimo ingênuo dizer que o feijão Embrapa 5.1 “deveria ser idêntico” a variedade de origem pois as manipulações necessárias para gerar o transgênico resultam em certas alterações que, se irrelevantes, são ignoradas e se deletérias são descartadas pelos cientistas. Se fizermos as mesmas análises, cujos resultados preocupam alguns, com as muitas variedades convencionais consumidas no país, as diferenças serão impressionantes e irrelevantes para a questão “segurança”.

Como já foi comentado anteriormente, não existe base factual (bioquímica ou genética) para imaginar que o feijão Embrapa apresente risco maior do que um feijão comum ou melhorado por mutagênese química ou física, que por sinal, não é supervisionado nutricional e molecularmente antes de sua comercialização. Sem base biológica, os testes tornam-se formalidades supérfluas e o ruído experimental, principalmente com amostras pequenas, quase inevitavelmente vai gerar resultados que são irrelavantes a menos que se amplie muito o número de animais (para amostras controle e transgênicas) além de ser prudente incluir animais alimentados com outros feijões convencionais para uma idéia realista do significado das variações detectadas. Imaginem o custo dessa busca “caça fantasma”, desencadeada simplesmente devido a uma aplicação pouco esclarecida do princípio da precaução. As preocupações sem base racional, levantadas a todo momento pelos que temem a tecnologia, se aplicariam com maior lógica aos produtos convencionais.

Caso isso aconteça, do dia para a noite estaria inviabilizada a produção agrícola do planeta. Por que não fazer estudos com Rhizobium e nodulação em todos os feijões comercializados? Por que não conduzir estudos nutricionais de longo prazo com os alimentos convencionais derivados de mutagênese? Qual a razão lógica que exclui essas preocupações com as plantas convencionais? Ou a razão seria metafísica? A alteração introduzida seria “contra a natureza”, algo como o pecado original, que, em muitas interpretações, consistiu apenas em comer o fruto da “árvore do conhecimento”? Recentemente 41 cientistas suecos da área vegetal lançaram um manifesto contra a sobre-regulação da genética moderna na Europa (reproduzido no blog GenPeace: genpeace.blogspot.com). Os autores observam que, fazendo um paralelo com as exigências para os produtos farmacêuticos, a “lógica da legislação atual sugere que apenas drogas produzidas por meio de engenharia genética deveriam ser avaliadas quando a efeitos indesejáveis”.

Instilar o medo com base em suposições não ajuda a proteger a população ou o meio ambiente. Marie Curie teria dito “Na vida nada deve ser temido. Mas tudo deve ser compreendido”. Considero irresponsável usar o “princípio da precaução” como alguns o fazem. Inclusive a OMS caiu nesta armadilha, classificando os telefones celulares no grupo 2B de risco para causar câncer. A radiação destes equipamentos é cerca de um milhão de vezes inferior à energia que pode produzir radicais livres e gerar dano ao DNA. A classe 2B inclui o risco de câncer relativo ao café, resíduos da queima de combustíveis fósseis e uso de dentadura…. O que a WHO manteve viva, irresponsavelmente, é a justificativa para a dúvida, que vai legitimar pesquisas caras e irrelevantes, cujo resultado será inconclusivo, como o mega estudo anterior. Incrivelmente mais perigoso é o uso do celular enquanto se dirige.

Francisco G. da Nóbrega é professor da Universidade de São Paulo (USP).

Genes, germs and the origins of politics (New Scientist)

NS 2813: Genes, germs and the origins of politics

* 18 May 2011 by Jim Giles

A controversial new theory claims fear of infection makes the difference between democracy and dictatorship

COMPARE these histories. In Britain, democracy evolved steadily over hundreds of years. During the same period, people living in what is now Somalia had many rulers, but almost all deprived them of the chance to vote. It’s easy to find other stark contrasts. Citizens of the United States can trace their right to vote back to the end of the 18th century. In Syria, many citizens cannot trace their democratic rights anywhere – they are still waiting for the chance to take part in a meaningful election.

Conventional explanations for the existence of such contrasting political regimes involve factors such as history, geography, and the economic circumstances and culture of the people concerned, to name just a few. But the evolutionary biologist Randy Thornhill has a different idea. He says that the nature of the political system that holds sway in a particular country – whether it is a repressive dictatorship or a liberal democracy – may be determined in large part by a single factor: the prevalence of infectious disease.

It’s an idea that many people will find outrageously simplistic. How can something as complex as political culture be explained by just one environmental factor? Yet nobody has managed to debunk it, and its proponents are coming up with a steady flow of evidence in its favour. “It’s rather astonishing, and it could be true,” says Carlos Navarrete, a psychologist at the Michigan State University in East
Lansing.

Thornhill is no stranger to controversy, having previously co-authored A Natural History of Rape, a book proposing an evolutionary basis for rape. His iconoclastic theory linking disease to politics was inspired in part by observations of how an animal’s development and behaviour can respond rapidly to physical dangers in a region, often in unexpected ways. Creatures at high risk of being eaten by predators, for example, often reach sexual maturity at a younger age than genetically similar creatures in a safer environment, and are more likely to breed earlier in their lives. Thornhill wondered whether threats to human lives might have similarly influential consequences to our psychology.

The result is a hypothesis known as the parasite-stress model, which Thornhill developed at the University of New Mexico, Albuquerque, with his colleague Corey Fincher.

 

 

Xenophobic instincts

The starting point for Thornhill and Fincher’s thinking is a basic human survival instinct: the desire to avoid illness. In a region where disease is rife, they argue, fear of contagion may cause people to avoid outsiders, who may be carrying a strain of infection to which they have no immunity. Such a mindset would tend to make a community as a whole xenophobic, and might also discourage interaction between the various groups within a society – the social classes, for instance – to prevent unnecessary contact that might spread disease. What is more, Thornhill and Fincher argue, it could encourage people to conform to social norms and to respect authority, since adventurous behaviour may flout rules of conduct set in place to prevent contamination.

Taken together, these attitudes would discourage the rich and influential from sharing their wealth and power with those around them, and inhibit the rest of the population from going against the status quo and questioning the authority of those above them. This is clearly not a situation conducive to democracy. When the threat of disease eases, however, these influences no longer hold sway, allowing forces that favour a more democratic social order to come to the fore.

That’s the idea, anyway. But where is the evidence?

The team had some initial support from earlier studies that had explored how a fear of disease affects individual attitudes. In 2006, for example, Navarrete found that when people are prompted to think about disgusting objects, such as spoilt food, they become more likely to express nationalistic values and show a greater distrust of foreigners (Evolution and Human Behavior, vol 27, p 270). More recently, a team from Arizona State University in Tempe found that reading about contagious illnesses made people less adventurous and open to new experiences, suggesting that they have become more inward looking and conformist (Psychological Science, vol 21, p 440).

Temporarily shifting individual opinions is one thing, but Thornhill and Fincher needed to show that these same biases could change the social outlook of a whole society. Their starting point for doing so was a description of cultural attitudes called the “collectivist-individualist” scale. At one end of this scale lies the collectivist outlook, in which people place the overall good of society ahead of the freedom of action of the individuals within it. Collectivist societies are often, though not exclusively, characterised by a greater respect for authority – if it’s seen as being necessary for the greater good. They also tend to be xenophobic and conformist. At the other end there is the individualist viewpoint, which has more emphasis on openness and freedom for the individual.

Pathogen peril

In 2008, the duo teamed up with Damian Murray and Mark Schaller of the University of British  Columbia in Vancouver, Canada, to test the idea that societies with more pathogens would be more collectivist. They rated people in 98 different nations and regions, from Estonia  to Ecuador, on the collectivist-individualist scale, using data from questionnaires and studies of linguistic cues that can betray a social outlook. Sure enough, they saw a correlation: the greater the threat of disease in a region, the more collectivist people’s attitudes were (Proceedings of the Royal Society B, vol 275, p 1279). The correlation remained even when they controlled for potential confounding factors, such as wealth and urbanisation.

A study soon followed showing similar patterns when comparing US states. In another paper, Murray and Schaller examined a different set of data and showed that cultural differences in one collectivist trait – conformity – correlate strongly with disease prevalence (Personality and Social Psychology Bulletin, vol 37, p 318).

Thornhill and Fincher’s next challenge was to find evidence linking disease prevalence not just with cultural attitudes but with the political systems they expected would go with them. To do so, they used a 66-point scale of pathogen prevalence, based on data assembled by the Global Infectious Diseases and Epidemiology Online Network. They then compared their data set with indicators that assess the politics of a country. Democracy is a tough concept to quantify, so the team looked at a few different measures, including the Freedom House Survey, which is based on the subjective judgements of a team of political scientists working for an independent American think tank, and the Index of Democratization, which is based on estimates of voter participation (measured by how much of a population cast their votes and the number of referendums offered to a population) and the amount of competition between political parties.

The team’s results, published in 2009, showed that each measure varied strongly with pathogen prevalence, just as their model predicted (Biological Reviews, vol 84, p 113). For example, when considering disease prevalence, Somalia is 22nd on the list of nations, while the UK comes in 177th. The two countries come out at opposite ends of the democratic scale (see “An infectious idea”).

Importantly, the relationship still holds when you look at historical records of pathogen prevalence. This, together with those early psychological studies of immediate reactions to disease, suggests it is a nation’s health driving its political landscape, and not the other way around, according to the team.

Last year, they published a second paper that used more detailed data of the diseases prevalent in each region. They again found that measures of collectivism and democracy correlate with the presence of diseases that are passed from human to human – though not with the prevalence of diseases transmitted directly from animals to humans, like rabies (Evolutionary Psychology, vol 8, p 151). Since collectivist behaviours would be less important for preventing such infections, this finding fits with Thornhill and Fincher’s hypothesis.

“Thornhill’s work strikes me as interesting and promising,” says Ronald Inglehart, a political scientist at the University of Michigan in Ann Arbor who was unaware of it before we contacted him. He notes that it is consistent with his own finding that a society needs to have a degree of economic security before democracy can develop. Perhaps this goes hand in hand with a reduction in disease prevalence to signal the move away from collectivism, he suggests.

Inglehart’s comments nevertheless highlights a weakness in the evidence so far assembled in support of the parasite-stress model. An association between disease prevalence and democracy does not necessarily mean that one drives the other. Some other factor may drive both the prevalence of disease in an area and its political system. In their 2009 paper, Thornhill and Fincher managed to eliminate some of the possible “confounders”. For example, they showed that neither a country’s overall wealth nor the way it is distributed can adequately explain the link between the prevalence of disease there and how democratic it is.

But many other possibilities remain. For example, pathogens tend to be more prevalent in the tropics, so perhaps warmer climates encourage collectivism. Also, many of the nations that score high for disease and low for democracy are in sub-Saharan Africa, and have a history of having been colonised, and of frequent conflict and foreign exploitation since independence. Might the near-constant threat of war better explain that region’s autocratic governments? There’s also the possibility that education and literacy would have an impact, since better educated people may be more likely to question authority and demand their rights to a democracy. Epidemiologist Valerie Curtis of the London School of Hygiene and Tropical Medicine thinks such factors might be the ones that count, and says the evidence so far does not make the parasite-stress theory any more persuasive than these explanations.

Furthermore, some nations buck the trend altogether. Take the US and Syria, for example: they have sharply contrasting political systems but an almost identical prevalence of disease. Though even the harshest critic of the theory would not expect a perfect correlation, such anomalies require some good explanations.

Also lacking so far in their analysis is a coherent account of how historical changes in the state of public health are linked to political change. If Thornhill’s theory is correct, improvements in a nation’s health should lead to noticeable changes in social outlook. Evidence consistent with this idea comes from the social revolution of the 1960s in much of western Europe and North America, which involved a shift from collectivist towards individualist thinking. This was preceded by improvements in public health in the years following the second world war – notably the introduction of penicillin, mass vaccination and better malaria control.

There are counter-examples, too. It is not clear whether the opening up of European society during the 18th century was preceded by any major improvements in people’s health, for example. Nor is there yet any clear evidence linking the current pro-democracy movements in the Middle East and north Africa to changes in disease prevalence. The theory also predicts that episodes such as the recent worldwide swine-flu epidemic should cause a shift away from democracy and towards authoritarian, collectivist attitudes. Yet as Holly Arrow, a psychologist at the University of Oregon in Eugene, points out, no effect has been recorded.

Mysterious mechanisms

To make the theory stick, Thornhill and his collaborators will also need to provide a mechanism for their proposed link between pathogens and politics. If cultural changes are responsible, young people might learn to avoid disease – and outsiders – from the behaviour of those around them. Alternatively, the reaction could be genetically hard-wired. So far, it has not proved possible to eliminate any of the possible mechanisms. “It’s an enormous set of unanswered questions. I expect it will take many years to explore,” Schaller says.

One possible genetic explanation involves 5-HTTLPR, a gene that regulates levels of the neurotransmitter serotonin. People carrying the short form of the gene are more likely to be anxious and to be fearful of health risks, relative to those with the long version. These behaviours could be a life-saver if they help people avoid situations that would put them at risk of infection, so it might be expected that the short version of the gene is favoured in parts of the world where disease risk is high. People with the longer version of 5-HTTLPR, on the other hand, tend to have higher levels of serotonin and are therefore more extrovert and more prone to risk-taking. This could bring advantages such as an increased capacity to innovate, so the long form of the gene should be more
common in regions relatively free from illness.

That pattern is exactly what neuroscientists Joan Chiao and Katherine Blizinsky at Northwestern University in Evanston, Illinois, have reported in a paper published last year. Significantly, nations where the short version of the gene is more common also tend to have more collectivist attitudes (Proceedings of the Royal Society B, vol 277, p 529).

It is only tentative evidence, and some doubt that Chiao and Blizinsky’s findings are robust enough to support their conclusions (Proceedings of the Royal Society B, vol 278, p 329). But if the result pans out with further research, it suggests the behaviours involved in the parasite-stress model may be deeply ingrained in our genetic make-up, providing a hurdle to more rapid political change in certain areas. While no one is saying that groups with a higher proportion of short versions of the gene will never develop a democracy, the possibility that some societies are more genetically predisposed to it than others is nevertheless an uncomfortable idea to contemplate.

Should the biases turn out to be more temporary – if flexible psychological reactions to threat, or cultural learning, are the more important mechanisms – the debate might turn to potential implications of the theory. Projects aiming to improve medical care in poor countries might also lead a move to more democratic and open governments, for example, giving western governments another incentive to fund these schemes. “The way to develop a region is to emancipate it from parasites,” says Thornhill.

Remarks like that seem certain to attract flak. Curtis, for instance, bristled a little when New Scientist put the idea to her, pointing out that the immediate threat to human life is a pressing enough reason to be concerned about infectious disease.

Thornhill still has a huge amount of work ahead of him if he is to provide a convincing case that will assuage all of these doubts. In the meantime, his experience following publication of A Natural History of Rape has left him prepared for a hostile reception. “I had threats by email and phone,” he recalls. “You’re sometimes going to hurt people’s feelings. I consider it all in a day’s work.”

Jim Giles is a New Scientist correspondent based in San Francisco