Tuesday, January 27, 2009

Darwin’s natural selection linked to disease resistance

By Marc Songini

Harvard University and MIT researchers are studying the effect of natural selection on human genomes and getting more detailed insight into the interplay between the human species and the diseases that afflict it.

This research was the subject of a presentation given last week at the Broad Institute at MIT during a Darwin Bicentennial Symposium. Some half-dozen speakers on Friday discussed Darwin’s effect in biology. Among the presenters was Pardis Sabeti, a professor at the Broad Institute and Harvard University, who gave a lecture on natural selection in humans and pathogens.

“Darwin is one of the founders of life sciences, and a great shaping force, although there are many naturalists and scientists before and after him that helped shaped the modern study, including Alfred Russell Wallace, J.B.S Haldane, and Gregor Mendell,” Sabeti said.

Sabeti’s research, which includes doing field work in Nigeria in Africa, involves understanding how different forces influence the genetic structure of humans and the pathogens that prey on them. “We are currently in the phase of going through the genome and finding the genetic variations that have arisen through evolution to enhance survival and reproductive success,” she said. “These include variations that protect from infectious disease, act against a changing environment and sun exposure, help in metabolism with changing diets.”

Sabeti’s genetics-related research is giving some insight into how certain traits, such as lactose tolerance, develop over time and in certain regions. For instance, lactose tolerance was developed rapidly in some humans over a period of about 10,000 years. All mammals drink milk from their mothers when young, she explained, but a lifelong tolerance for milk wasn’t historically normal. At some point, all mammals need to wean, or the mother cannot ovulate and have other offspring. Some humans, however, began to rely on cows and milk products over time, allowing the lactose-tolerant genes to become predominant, said Sabeti. Her work is about trying to precisely define how all these mechanisms come to work together to enable the adaptation.

Similar research is being applied to understand why some people exhibit resistance to Lassa fever virus, malaria, and other diseases, she explained. Contrarily, researching the genetics of the diseases themselves, or mosquitoes, and how they are able to exhibit resistance over time to antibiotics or DDT also can provide valuable insights. There is a ways to go, however, before this research will yield concrete results.

“Once we identify and elucidate these variations,” said Sabeti, “we might potentially be able to develop therapies that use these insights.” That might include creating a drug that blocks a receptor they have identified to be involved in viral pathogenesis. “But we are only at the beginning of this long and exciting process,” she said.