Monday, October 31, 2011

Canoodling with cavemen gave healthy boost to human genome, study finds

AUG. 25, 2011
Canoodling with cavemen gave healthy boost to human genome, study finds
Stanford School of Medicine

Laurent Abi-Rached, Paul Norman and Libby Guethlein are co-authors of research on how the genome of geographically-distinct human populations vary in the amount and type of immune-system genes inherited from evolutionary cousins, the Neanderthals and Denisovans. People in Papua New Guinea, for instance, have a particularly high percentage of one type of immune-system gene that is rarely found in people in Africa.

For a few years now, scientists have known that humans and their evolutionary cousins had some casual flings, but now it appears that these liaisons led to a more meaningful relationship.

Sex with Neanderthals and another close relative — the recently discovered Denisovans — has endowed some human gene pools with beneficial versions of immune system genes, report researchers at the Stanford University School of Medicine in an article published online Aug. 25 in Science Express.

Although modern humans, Neanderthals and Denisovans share a common ancestor in Africa, the groups split into separate, distinct populations approximately 400,000 years ago. The Neanderthal lineage migrated northwestward into West Asia and Europe, and the Denisovan lineage moved northeastward into East Asia. The ancestors of modern man stayed in Africa until 65,000 years or so ago, when they expanded into Eurasia and then encountered the other human-like groups. In some cases, the rendezvous were amorous in nature.

Last year, a partial genome sequence of Neanderthals, who died out approximately 30,000 years ago, revealed that these trysts left as much as 4 percent Neanderthal DNA in the genetic blueprint of some present-day humans. Last December, the genome of another human cousin, the extinct Denisovans, made clear that up to 6 percent of some people's genomes are Denisovan in origin.

Now, a team of researchers led by Peter Parham, PhD, professor of structural biology and of microbiology and immunology, has found that these matings had a positive effect on modern human fitness. "The cross breeding wasn’t just a random event that happened, it gave something useful to the gene pool of the modern human," said Parham, who is senior author of the study.

The useful gift was the introduction of new variants of immune system genes called the HLA class-1 genes, which are critical for our body's ability to recognize and destroy pathogens. HLA genes are some of the most variable and adaptable genes in our genome, in part because the rapid evolution of viruses demands flexibility on the part of our immune system.

"The HLA gene system, with its diversity of variants, is like a magnifying glass," said lead author Laurent Abi-Rached, PhD, explaining that it provides a lot more detail about the history of populations than typical gene families. Abi-Rached is a research associate in the Parham lab.

Prior to the sequencing of the Neanderthal and Denisovan genomes, Parham and his group had suspected that at least one HLA variant came from archaic humans. They determined that the variant known as HLA-B*73 is rare in present-day African populations but occurs with significant frequency in West Asian populations. The ethnic distribution of HLA-B*73 and its similarity across populations suggested that it came from a relatively recent co-mingling of modern human and archaic human DNA, which most likely would have happened outside of Africa. Parham's team wanted to discern which archaic humans were the source of the HLA-B*73 gene type. In the last year they have found the answer in the genome sequence of a recently discovered human relative, the Denisovans, whose existence first came to light in 2008 with the discovery of an unfamiliar finger bone and tooth in a cave in Siberia...

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