Molly Przeworski constructs time machines. Built with math and fueled by genetics, they offer sweeping views of the past, present, and even future of genetics and evolution.
Entering college, Przeworski was drawn to logic and philosophy but didn’t have a clear idea of what she wanted to study. A class in mathematical biology caught her attention. The course used equations to study population dynamics and ecology; Przeworski was hooked.
“I like that you can use mathematical models to get at questions that you might not think you can get at, like how humans and chimps split, or what the human population size was in the past,” says Przeworski, now a population geneticist at the University of Chicago. “These seem like science fiction questions. At first it appears they're not answerable. But if you use the right models and think about them the right way, you can find answers.”
Over the past decade, Przeworski has helped anchor her once theory-bound field on more solid, data-driven ground. As a graduate student, she and a fellow student found that the human population was fairly stable until the introduction of agriculture about 10,000 years ago, bucking earlier theories of steady growth through the eons. More recently, her studies of great ape populations confirmed that three geographically separate subspecies of chimpanzees are genetically distinct—a finding with implications for the species’ survival. “Finding the pockets of diversity helps focus conservation efforts,” says Przeworski.
The work she enjoys most, though, involves probing the mysteries of genetic recombination, the gene-shuffling process essential to sexual reproduction—and to evolution. During recombination, parental chromosomes swap pieces, creating genetic variants; it is the reason no two siblings, except for identical twins, are exactly alike. Without that variation, natural selection would not be possible.
By comparing the genomes of humans and chimpanzees, Przeworski found that recombination occurs with varying frequency, and in different genomic locations, in the two species—a surprise, given their relatedness.
These days, Przeworski has turned her attention back to human biology with research that could someday help prospective parents understand their risk for producing unhealthy embryos. Errors in recombination can create too many chromosomes, resulting in a condition, called aneuploidy, that is the leading cause of miscarriages and developmental disabilities.
Already, her work has confirmed that women who experience high amounts of recombination tend to have more children—one clue to unraveling the connection between an individual’s genetics and her chances of producing an embryo with aneuploidy. But it also points to a deeper evolutionary truth: Recombination, a crucial biological process, is highly variable among individuals. “I’m really interested in trying to figure out how something so fundamental can also vary so much,” says Przeworski.
Przeworski also serves as an analyst for the 1,000 Genomes Project, a global effort to map human genetic diversity and link genetic variation to disease. “I got my Ph.D. less than 10 years ago, and we didn’t have a single human genome sequenced. Now we’re around the corner from having 1,000 of them. With all these data, the challenge is trying to figure out what to look for, to find the signals that will help us answer the big questions.”