Beyond the Genome: Uncovering evolution’s driving forces in the human genome

Leah Eisenstadt, November 3rd, 2010 | Filed under
  • The ability to digest cow's milk is an example of positive selection
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Last week, here on the blog we told you about some of the exciting results to come from the recently completed pilot phase of the 1000 Genomes Project. Scientists in the consortium sequenced several hundred genomes and captured even more of the variation among human genomes than had been previously known. The project aims to not only employ “next-generation” sequencing technologies at a scale never before achieved, it also aims to create the best map of human genetic variation so far.

That map is already being put to use by other scientists. At the recent Beyond the Genome conference in Boston, Shari Grossman, a researcher in the Broad Institute’s Infectious Disease Initiative and Program in Medical and Population Genetics, presented results from her team’s latest efforts to uncover signs of evolution in the human genome. With her advisor, Pardis Sabeti, Grossman and a team of other researchers at the Broad mined data from the 1000 Genomes Project to look for regions of the genome that confer some advantage to the organism, regions said to be under “positive selection.” A mutation arises in one person’s genome and, if it improves that person’s chances of survival and ability to reproduce, it quickly becomes widespread in a population. This pattern leaves a genetic “footprint” that scientists can hunt by analyzing the sequence of a genome.

An example of a gene under positive selection is the mutation that allows adults to digest milk. Thousands of years ago, adults did not have the ability to drink cow’s milk. But as cows were introduced to Europe, people with a certain mutation that enabled them to break down lactose sugars in milk could use cow’s milk as a food source, offering them a significant survival advantage. The mutation quickly spread through the population and today, most European adults can drink milk. (Those who can’t suffer from “lactose intolerance.”)

Uncovering advantageous mutations, and the biological pathways they impact, gives scientists a unique view of human history, and can shed light on traits and diseases. So far, the researchers have uncovered genes under selection that are involved in biological processes known to be targets of selection, such as infectious disease, skin pigment, metabolism, and hair and sweat.

As Grossman explained, the team takes a four-step approach: 1) detect the region of the genome under selection — the region that harbors the genetic mutation that confers an advantage, 2) narrow down the candidate region to the specific gene under selection, 3) pinpoint the mutation in that gene that is advantageous, and 4) uncover the functional consequences of that mutation – how that mutation changes the resulting protein and alters its function.

With fully sequenced genomes becoming available from the 1000 Genomes Project, Grossman and her colleagues can more deeply mine the human genome for genetic mutations that are under selection. Grossman explained that the completion of the 1000 Genomes pilot is “one of the most exciting things that’s happened lately.” She added, “It allows us to have a full set of variants and look through these regions to identify functional mutations.” As more and more fully decoded genomes come to light, they will help reveal the genetic factors that drive human evolution and, therefore, play important roles in human biology.

Other Broad researchers contributing to this work include Ilya Shlyakhter, Elinor Karlsson, Shervin Tabrizi, Kristian Andersen, John Rinn, Eric Lander, and Steve Schaffner.

Stay tuned for more of our coverage from the recent Beyond the Genome Conference in Boston.