The evolution of genetic variation

  • May 28, 2012
The evolution of genetic variation

Variations in DNA coding are more common than thought, according to new research.

One-letter switches in the DNA code occur much more frequently in human genomes than anticipated, but are often only found in one or a few individuals, according to new research published in the online edition of Science.

Researchers, including Gates alumnus Timothy O’Connor, found that the explosion in human population over the last 5,000 years has profoundly influenced genetic variation patterns.

Their paper, “Evolution and Functional Impact of Rare Coding Variations from Deep Sequencing of Exomes,” describes their study of the protein-coding sections of genomes from almost 2,440 individuals from European or African extraction.

The study is described as a first step towards understanding how rare genetic variants contribute to some of the leading chronic illnesses in the world.

It was conducted as part of the mission of the Seattle GO at the University of Washington and the Broad GO at Harvard University and MIT, both funded by the National Institute of Health’s National Heart Lung and Blood Institute Exome Sequencing Project.

The researchers sequenced and compared 15,585 human protein-coding genes. They found more than a half-million single-letter DNA code variations in their sample populations. The majority of these variations arose recently in human evolutionary history and so were rare, novel, and specific either to the African or European study populations.

They then focused on single-letter variations in the DNA that might affect the functions of proteins and be linked to specific diseases such as heart attacks before old age. They estimated that just over two per cent of the approximately 13,600 single nucleotide variations each person carried on average influenced the function of about 313 genes per genome. More than 95 percent of the single-letter code changes predicted to be functionally important were found to be rare.

The scientists calculated the average number of novel, single-letter code variations in their study subjects and found 549 per individual overall. People of African descent had about twice the number of new variations compared to those of European descent, or 762 versus 382.

The researchers also measured the effects of natural selection on rare coding variation.

They called for more powerful tests to detect the effects of rare genetic variations on human health and said that large sample sizes will be required to associate rare variants with complex traits.

Explaining the significance of the research, Tim O’Connor [2007] said: “It shows that we must integrate evolutionary theory into our understanding of complex genetic diseases.  For example, heart disease in one population may have a completely different genetic underpinning than in another population. We may need to re-evaluate some of the assumptions we make in population genetics analyses to better accommodate rare genetic variants as now we know they are abundant and potentially important.”

Tim did his PhD in Zoology with the support of a Gates Cambridge scholarship and is currently based at the University of Washington.

Picture credit: Sheela Mohan and www.freedigitalphotos.com

Latest News

Lifetime honour for former Provost

Professor Barry Everitt, former Provost of the Gates Cambridge Trust, has been elected a lifetime Fellow of the American Association for the Advancement of Science (AAAS) the world’s largest general scientific society and publisher of the Science family of journals. AAAS has elected more than 500 scientists, engineers and innovators from around the world and […]

‘Tackle climate change misinformation through computational social science’

Future leaders and researchers need to be urgently trained to tackle climate change misinformation through an interdisciplinary approach that foregrounds computational social science and extends beyond laboratories and university campuses to shape the science-policy interface and rebuild public trust in climate research, according to leading academics. Writing in Nature Human Behaviour, the academics, including Dr Ramit […]

An existential psychological thriller for aesthetes

Christy Edwall’s first novel, History Keeps Me Awake at Night, out in early February, has been described as “an existential psychological thriller for aesthetes and lovers of cultural London and the world… A story cleverly told of a young woman involved in contemporary forms of global voyeurism”. It tells the story of Margit, a London […]

A detective of ancient climate change

Stijn De Schepper is an ancient detective. His job is to investigate past climate change through working his way down the ocean bed, starting with today’s sediment and moving back through thousands of years of Earth’s history.  He maps ancient marine sediments to find out if, why and how the environment changed in the past. […]