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Adaptive changes in the genome may provide insight into the genetics of complex disease

esearchers describe the largest signature of natural selection discovered to date: a series of four contiguous genes on Chromosome 7 that appear to have been transformed as people in Europe began to drink more cow and goat milk. The result: people that inherited certain variations of these genes, known as alleles, are better able to absorb calcium into their bodies.

One of the genes involved is TRPV6 and has been implicated in the development or aggressiveness of prostate cancer. It and another gene in the region, TRPV5, are also involved in calcium absorption in the kidney, intestine and placenta. Scientists had previously found that genetic variation in a gene promoting lactose-tolerance in milk drinking European populations was selected for some 10,000 to 20,000 years ago. The latest discovery seems to complement that discovery, Akey said, because the body would not only need to be tolerant to lactose but also be able to absorb the calcium.

The lead author of the paper says that researchers worldwide are just beginning to understand evolution's contribution to our genetic risks for disease and the underlying genetic causes of illness.

"This paper provides compelling evidence that identifying regions of the human genome that have been the targets of natural selection will provide important insights into recent human evolutionary history and may also help us understand and identify the genetic contribution to various complex diseases," Akey said.

The findings appear to provide support for a theory widely known as the 'thrifty gene hypothesis' that was originally proposed to explain the high prevalence of Type 2 diabetes. The thrifty gene hypothesis argues that genetic variation that encouraged people to eat and store lots of food was beneficial at one point in human history when resources were scarce, but is now detrimental and increases susceptibility to diseases such as diabetes a
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Contact: Walter Neary
wneary@u.washington.edu
206-685-1323
University of Washington
8-Sep-2004


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