Team Tracks Evolution in Genome

A team of scientists, led by a third-year Harvard Medical School student, has developed the first powerful tool to study how the human genome has been affected by cultural and environmental factors over the past 10,000 years.

The method, known as the long-range haplotype (LRH) test, allows biologists to detect the process by which a gene that is favorable to survival becomes more frequent in a population—a process called positive gene selection.

This advance holds significant implications for the study of human disease and its treatment, according to Pardis C. Sabeti, the medical student who led the study.

“We can now find genes that protect against certain diseases and look into increasing expression of these [genes] as drug therapy,” she said.

Sabeti and her team have already used the LRH test to identify the positive selection of two genes associated with resistance to malaria, a life-threatening parasitic disease transmitted by mosquitoes.

The research, conducted at the Whitehead Institute and MIT Center for Genome Research, was published online this week in the journal Nature.

Sabeti and her co-authors gathered genetic samples from men in Africa, where 90 percent of the world’s malarial deaths occur, as well as from subjects in Europe and East Asia.

Gene combinations containing two forms of genes that offer partial protection against malaria were found to be statistically common in African populations but absent in populations outside the continent.

Both forms exhibited evidence of positive selection.

The LRH test assesses the ages of gene combinations by measuring their association with nearby genes, which decreases with time. This measurement is known as a linkage disequilibrium.

A gene that has been positively selected shows an unusually large decrease over time given its population frequency.

Because there are so few genetic variations between individual humans, until now researchers had been unable to gather data on genetic change.

“It’s been really, really, really hard in the past to detect evidence of natural selection [in humans],” said co-investigator David E. Reich ’96, who is also a tutor in Lowell House. “We now have an unprecedented detailed picture of variation patterns.”

The next step, according to Reich, will to be to scan entire human genomes in search of other positively selected genes.

—Ishani Ganguli can be reached at ganguli@fas.harvard.edu.