It’s intriguing to find the roots of physical traits: skin color, height, and those weird tufts of hair on Uncle Mike’s ears. We’re all curious to know why we look the way we do. But new technologies are allowing us to discover the precise genetic roots of human traits that vary across the world. Variations in our DNA have helped us resist diseases and adapt to different climates and foods, enabling us to colonize just about every environment on the planet.
Recent studies have pinpointed variations responsible for lighter skin in Northern climates (such as SLC24A5 ) and the ability to tolerate milk sugar (lactose) in adulthood . But a new NIH-funded study of a gene variant that arose in China adds a fascinating wrinkle—the use of a mouse model to help understand a potential human advantage . (Regular readers will note that last week in this space I wrote about how mouse models could sometimes be misleading—this week the mouse is a champion!)
The lead author of this new report, Pardis Sabeti, is a geneticist at the Broad Institute in Cambridge, MA, and also happens to be a fine musician (check out thousanddays.com). I had fun in a musical jam with Pardis a couple of years ago. But more importantly for today’s blog, Dr. Sabeti is a NIH Director’s New Innovator Awardee and has been mining through the growing database of genome sequences from people all over the world, searching for key genetic mutations in recent human evolution (the last 100,000 years) that show evidence of positive selection.
This search led Sabeti and her international team to the Ectodysplasin A Receptor (EDAR), an ancient gene that seems to be involved in development of teeth and hair. Africans and Europeans carry the same version of EDAR, but a variant called V370A (that means the amino acid valine is replaced by alanine at position 370 in the protein) is present almost exclusively in East Asian and Native American populations—suggesting some sort of turning point in human evolution. According to Sabeti’s reconstructions, this variant arose in Central China about 30,000 years ago and spread rapidly though the East Asian population, suggesting that it conferred an environmentally advantageous or sexually selected trait.
So what exactly does this V370A variation in the EDAR gene do? With so much additional variation in the human population, the effect of this one variant would be hard to nail down. So instead, the researchers created mice that either carried the normal spelling or the East Asian V370A variant. (Otherwise the mice were all effectively identical twins, because they were derived from an inbred strain.)
When the researchers examined the V370A mice, they found thicker hair and a higher density of sweat glands in the skin. They then tested people of Han Chinese descent and found that they did indeed have thicker hair (which had been noticed previously) and also they had significantly more sweat glands—a real surprise!
So what’s the selective advantage of V370A? Well, China was a pretty warm place 30,000 years ago, so more sweat glands might have helped cool the body. But alternatively, a preference for certain physical traits, including lush thick dark hair, might have influenced mate choice.
The EDAR gene is just one of about 400 genetic regions being studied by Dr. Sabeti’s group that seem to be important in recent human evolution. Which traits do they control? What stories can they tell us about human history? And how have they shaped our evolution?
 SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, O’donnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC. Science. 2005 Dec 16;310(5755):1782-6.
 Identification of a variant associated with adult-type hypolactasia. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I. Nat Genet. 2002 Feb;30(2):233-7. Epub 2002 Jan 14.
 Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, Yang Y, Li S, Tang K, Chen H, Powell A, Itan Y, Fuller D, Lohmueller J, Mao J, Schachar A, Paymer M, Hostetter E, Byrne E, Burnett M, McMahon AP, Thomas MG, Lieberman DE, Jin L, Tabin CJ, Morgan BA, Sabeti PC. Cell. 2013 Feb 14;152(4):691-702.
NIH support: the National Institute of General Medical Sciences; the National Human Genome Research Institute; and the National Center for Advancing Translational Sciences