HARVARD GAZETTE ARCHIVES

Wakeley's recent work has simplified the complex calculations concerning gene frequencies in different groups in a population. He has shown that using averages of the gene frequencies gives results similar to more complex calculations using specific values. (Staff photos Maggie Mastricola/Harvard News Office)

John Wakeley is devising new ways to trace the evolutionary road taken by humans and the creatures with whom we share planet Earth by creating new models that examine how DNA has changed over time.

A theoretical population geneticist, Wakeley's research focuses on how our DNA changes as it is passed from generation to generation. He is examining how the tendency of humans to live in groups separated by ethnicity or by physical barriers like mountains and rivers affects DNA's random changes.

Understanding groupings of individuals can be critical to figuring out why our DNA carries particular patterns today. That's because changes in patterns of genetic variation due to genetic drift - one of the major forces behind evolution - occur more rapidly in smaller populations and subpopulations.

"What I've done is investigate the role of population subdivision and migration [on human evolution]," Wakeley said.

Wakeley: 'We use genetic markers to make inferences about population history.'

In his calculations of how genetic variation changes over time, Wakeley has created mathematical models that factor in the effect of smaller groups, called "demes" by geneticists. His work concerns "coalescent theory," which looks at the history of genes in a population.

While each piece of the human genome can be traced back to a common ancestor, such as the "mitochondrial Eve" from whom all the DNA in cell mitochondria are derived, Wakeley said such studies provide only a small picture of human history. If we were to trace back to common ancestors across the entire genome we'd find that certain parts would trace to one individual and others would trace to other individuals who lived in different places at different times.

"We use genetic markers to make inferences about population history," Wakeley said. "If we look at [the history of] one locus, we'll get a snapshot. If the aim is to understand the whole of human history, you need more than one picture of it. The only way to do that is to sample lots and lots of different genetic markers."

Wakeley's recent work has simplified the complex calculations concerning gene frequencies in different groups in a population. He has shown that using averages of the gene frequencies gives similar results as more complex calculations using specific values. He is also putting the finishing touches on a textbook on coalescent theory, which he hopes to complete this year.

Wakeley was appointed professor of organismic and evolutionary biology in July. Prior to that, he was the Thomas D. Cabot Associate Professor of Biology. He came to Harvard in 1998 as an assistant professor.

The son of a geologist and a psychologist, Wakeley recalls a love of biology from his earliest years. He credits his career choice to his undergraduate adviser, Marcus Feldman, a population geneticist at Stanford University. Wakeley received a bachelor's degree in biology at Stanford in 1989, went on to receive his doctorate at the University of California, Berkeley, and conducted postdoctoral research at Rutgers University.

"He made a really big impression on me," Wakeley said of Feldman.

Wakeley was attracted to genetics research because it seeks to answer fundamental questions about who humans are and how we got here. The fact that part of the answer is due to the randomness of genetic mutation and drift, and the random assortment of chromosomes into gametes - egg and sperm cells - during meiosis just makes it all the more intriguing, Wakeley said.

"I find genetics overall very compelling because of its connection with ancestry and meaning in humans," Wakeley said. "I think of things in stochastic terms, in terms of randomness. It's the way I see the world working a lot of the time."

alvin_powell@harvard.edu

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