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Selective Pressure and Infectious Disease

  • Title: Assistant Professor, Harvard University
  • Education: D. Phil, University of Oxford, 2002; MD, Harvard Medical School, 2006
  • Recommended by: Russ Altman

Pardis Sabeti has almost never taken a breather from studying. Since completing her under-graduate studies at MIT in 1997, she has received a master’s degree and a doctorate from the University of Oxford and a medical degree from Harvard Medical School. All the while, she has busily been churning out papers for Nature, Science, and PLoS Biology that tackle positive selection pressures, especially relating to humans.

Working with Eric Lander, who has been her advisor since her undergrad days, Sabeti developed a method to look for areas of the genome under selective pressure. The long haplotype approach, Sabeti says, is a way to scan the genome to look for genes that have recently spread through the human population, such as lactose tolerance or protection from malaria. “I look for adaptations, things that are beneficial, that spread through populations,” she says. The tools she works with work with populations as far back as 30,000 years ago, though 10,000 years ago is the sweet spot.

Sabeti not only studies humans, but also infectious diseases, applying the same thought processes to malarial evolution. “What are the things that are beneficial in the malaria genome that keeps it surviving?” she wonders.

From all these genomic studies, there are mounds of data to sift through and interpret. Once information has been teased out of the data, Sabeti is left with genes that appear to be under selection, but often there is no biological information about what those genes do. “Creating an entire platform that we use to go from studying these populations all the way down to getting the functional change that’s important and what it is that’s driving the selection is a challenge,” Sabeti says.

Looking ahead

Over the next few years, researchers should be able to draw a coherent picture of human evolution, says Sabeti. Gene variants could be tied to their underlying traits that feel the pressure of selection, and then those traits could be followed up on biologically, to get a sense of what drives human adaptation. “It’s a race to analyze the data,” she says. “There’s plenty to do for many, many years.”

In parasites, that same data analysis and information synthesis could go toward a method to eradicate parasitic diseases, such as malaria. “It’s one piece of the puzzle to understand: what are the tricks that this parasite has? How is it evolving? How is it adapting? What are the drug regimens we can use? How are the vaccines? How can we put all the pieces together in order to keep it down, or ideally, finally [eliminate] it?” she says.

Publications of note

In 2006, Sabeti, along with her colleagues, published a paper in Science that reviewed the ways of detecting positive natural selection in humans. While in the thick of wading through all the literature from Darwin and Wallace to the HapMap project, Sabeti wasn’t sure writing a review paper was a good idea. “It was like taking a very dense course in natural selection in order write that review,” she says. That dense course, she later realized, gave her the clarity of thought needed to lay the foundation for her 2007 Nature paper. In this research article, Sabeti and her colleagues identified human genes that have recently undergone positive selection. Specifically, they found two genes in West African populations linked to Lassa virus infection, two genes in Europeans related to skin pigmentation, and, in Asian populations, genes relevant to hair follicle development.

And the Nobel goes to…

If Sabeti were to win a Nobel Prize, she’d like it to be for curing an infectious disease — and she doesn’t want to take all the credit. “I would love the community to get a Nobel Prize for curing malaria, for sure,” she says.

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