The Flawed Premise of the HapMap

There's an interesting exchange afoot regarding the study of genetic variation among human populations. First, Nick Wade of the NYT wrote a piece on Duke geneticist David Goldstein whom I had the opportunity to hear speak earlier this year at the Yale Symposia on Health and Disease. Goldstein's talk then was on Pharmacogenetics, but now he has a few things to say on the $3 billion effort to decode the human genome. The major premise of the human genome project was that it would enable the discovery of the variant genes that predispose people to common diseases like cancer and Alzheimer’s.

“It’s an astounding thing,” Dr. Goldstein said, “that we have cracked open the human genome and can look at the entire complement of common genetic variants, and what do we find? Almost nothing. That is absolutely beyond belief.”

John Hawks points out, yeah that's exactly what we evilutionary biologists expected! Hawks writes "Of the variants that have been found in these genome-wide association studies, for Alzheimer's, Type 2 diabetes, schizophrenia -- a significant number appear to have been recently selected. So even these few that have been found wouldn't have been predicted under the "common variant" model. But most variants that cause senescence must be rare. That's Medawar's theory. Or they may be balances. That's Williams' theory. This is a case where modern evolutionary theory gives very clear predictions, which have now been confirmed at enormous cost."

Hawks refers to evolutionary icons Peter Medawar and George Williams, whose work on the evolution of senescence in the 50's seems to have been overlooked.

Oh well, the physicists got their LHC to look for the (probably) mythical boson; we got 3 billion to catalog the (almost) infinitely diverse human genome. Hawks says it best, "Recent human evolution is not progress toward a pinnacle. The human population is a snowdrift where ten thousand trade-offs have blown together, mostly by the luck of mutations."

Larry Moran, Daniel MacArthur, Dieneke, Razib and Jonathan Eisen also comment in their respective blogs.