"We want to understand where and how natural selection occurs," says Dr. Mark Shriver, associate professor of anthropology at Penn State. "However, most changes in genes are neutral and caused by the demographic history of the population."
Neutral demographic changes in populations occur because separated populations drift apart, decimated populations expand from smaller gene pools, and populations mix with each other.
Most individual mutations that occur in the genetic code are neutral or benign. These changes have no impact on the survival fitness of the individual and remain or disappear by chance. Some mutations destroy the ability of that part of the code to do its job, and the individual does not survive or reproduce relative to other members of the population. These individuals are generally selected out of the population because they are less fit. Other mutations accidentally provide a change that makes individuals more fit for their environment and gives them an advantage. These individuals are more fit and reproduce more, increasing the prevalence of that particular trait in the population.
"To identify genes that were naturally selected, it is important to know the demographic history of the populations being studied," says Shriver.
Researchers at Fred Hutchinson Cancer Research Center in Seattle created demographic models of possible population histories and applied them to genetic information from two populations - one African-American and the other European-American - sequenced at the University of Washington, Seattle. The four models represented populations that expanded exponentially, rapidly decreased to a small population size causing a bottleneck and then increased, where separated with only small amounts of interbreeding and split completely.
The researchers, who included Shriver; Joshua M. Akey, Fred Hutchinson Cancer Research Center; Mark J. Rieder, Christopher S. Carlson and Deborah A. Nickerson, University of Washington; and Leonid Kruglyak, Howard Hughes Medical Institute and Fred Hutchinson, reported in today's (Sept. 8) issue of the journal Public Library of Science - Biology, that the African-American population fits best the expansion model and the European-American population fits best the bottleneck model.
After the demographic models suggested the structure of the populations, the researchers looked at the possible areas where natural selection occurred. They looked at 132 genes from 24 African Americans and 23 European Americans. These genes were originally sequenced because they all have something to do with the inflammation immune response. Some of these genes are known to affect risk of genetic disease, but most are not associated with genetic diseases.
"It is very difficult to see a compelling signature of natural selection if we look at only one gene, but if we look at many related genes, it becomes easier to identify," says Shriver. "We found a cluster of four genes that appear to be heavily selected." This 115-kilobase region shows many signs of a recent selective sweep, but only in the European-American population. Recent for geneticists is something like 20 to 25,000 years ago. One hypothesis of human population movement suggests that a small number of humans moved out of Africa and populated the rest of the world. This scenario fits the idea of a European population that had a bottleneck - the small population leaving Africa.
This small population was also exposed to a large amount of new environmental pressures, while the African population may already have been adapted to its African environment at these particular genes. Shriver emphasized that, "It is notable that there are a number of genes where African populations are known to have undergone recent natural selection and so it is a hasty generalization to conclude that more changes are found out Africa.
"The European-American population was challenged by more new things in its environment," says Shriver. "And this challenge is reflected in adaptation to new parasites or new environmental factors."
The researchers cannot identify an individual gene in the cluster of four that was selected, but one of the genes, TRPV6 might be involved in susceptibility to aggressive prostate cancer and since there is a large difference in the prevalence of prostate cancer between the European- and African-American populations, TRPV6 may be the selected gene. TRPV6 and TRPV5 are involved in calcium absorption. Northern Europeans have been nearly universally selected for a tolerance for milk, while African and other populations have a high degree of lactose intolerance. The ability to drink large amounts of milk has been strongly selected in Northern Europeans since about 9,000 years ago when dairy-producing animals were domesticated. The researchers suggest that perhaps a need for more calcium because of changes in TRPV6 and TRPV5 pushed the selection of milk tolerance.
Tracking natural selection does not just illuminate adaptation to new dietary possibilities like milk drinking but can also help in mapping genes underlying complex human diseases.