Mining the human genome for signs of recent selection

By scanning the entire human genome in search of genetic variations that may signal recent evolution, University of Chicago researchers found more than 700 genetic variants that may be targets of recent natural positive selection during the past 10,000 years of human evolution.

In one of the first comprehensive genome scans for selection, the researchers found widespread evidence of evolution in all of the populations studied. Their results are published and freely available online in the open-access journal PLoS Biology.

The data analyzed here were collected by the International HapMap Project and consist of genetic data from 209 unrelated individuals who are grouped into three distinct populations: 89 East Asians, 60 Europeans and 60 Yorubans from Nigeria. The researchers found roughly the same number of signals of positive selection within each population. They also found that each population shares about one fifth of the signals with one or both of the other groups.

“This approach allows us to take a broad prospective to see what kinds of biological systems are undergoing adaptation,” said Jonathan Pritchard, professor of human genetics and corresponding author of the paper. “There have been a lot of recent changes—the advent of agriculture, shifts in diet, new habitats, climatic conditions—over the past 10,000 years, and we’re using these data to look for those signals of very recent adaptation.”

Among the more than 700 signals the team found were previously known sites of recent adaptation, such as the salt-sensitive hypertension gene and the lactase gene—the strongest signal in the genome hunt. The lactase mutation, which enables the digestion of milk to continue into adulthood, appeared in approximately 90 percent of Europeans.

“Presumably,” Pritchard said, “a few thousand years from now, if selection pressure remains the same, everyone will have [the selected mutation].”

Classifying all the genes by their biological functions, the researchers listed the top 16 categories that had the strongest signals, including olfaction (the sense of smell), reproduction-related processes and carbohydrate metabolism, which includes the lactase gene.

Other processes that show signals of selection include genes related to metabolism of foreign compounds, brain development and morphology. For example, the researchers found five genes involved in skin pigmentation that show evidence of positive selection in Europeans. “Only one of these five signals was known before,” Pritchard said. The authors also found signals of reproductive selection and sexual competition in all three populations.

“Many of the signals, however, seem to be more specific to modern human adaptation,” he said, “like skin pigmentation, which may respond to changes in habitat, or metabolism genes, like lactase, which may respond to changes in agriculture.”

The study was funded by the National Institutes of Health.