To honor his recent election to the National Academy of Sciences, we’re featuring Dr. Montgomery Slatkin of the University of California, Berkeley. Dr. Slatkin is known for his work in theoretical population genetics, in particular with regard to gene flow and range expansion. Recently, he’s also studied the genetics of human disease, and the paleo-genetics of ancestral human populations. Below, I ask Dr. Slatkin about his background, research and dinner parties.
1) Congratulations your election to the National Academy of Sciences! Can you tell us a bit about how you become a population geneticist?
When I was a graduate student in applied math at Harvard, I got to know William Bossert, who had just joined the faculty there. He asked for my help with some mathematical problems that arose in his studies of assortative mating. After I expressed some interest in the general subject, he arranged for me to meet E. O. Wilson and Ernst Mayr, both of whom encouraged me to work in in population genetics and evolution. It seemed like a great opportunity for me and they were all generous in helping me get started.
2) You’ve done considerable work on the estimation of gene flow among populations. Can you generally explain why the study of gene flow is important?
As Bossert first pointed out to me, gene flow is important for evolution because most populations have a broad spatial distribution and experience different conditions in different parts of their ranges. The kind of mathematics I had studied was well suited to the analysis of gene flow combined with other population genetic forces.
3) How has our ability to accurately estimate gene flow between populations improved? What do you see as remaining challenges?
More accurate estimates of the rates and patterns of gene flow are now available because of the vast increase in the amount of genetic data available and the many sophisticated methods of data analysis that have been developed. Many challenges remain. Much of population genetic analysis assumes some kind of equilibrium but many and probably most populations are not at an equilibrium. The interaction of gene flow and local populations density is not well accounted for. We will need better ways to assess how closely the simplified models used in population genetics conform to real populations. We still don’t know when gene flow will be a conservative force that constrains evolution and when it is a creative force that promotes evolution that would not occur in a single population.
4) Recently, you’ve been working with paleo-DNA samples from Neanderthals and Denisovans. What do you find most interesting about this work?
The Neanderthal and Denisova genome projects have provided an opportunity to develop and apply population genetics theory to data in a way that has helped discover previously unknown events in the history of modern humans. That kind of use of population genetics was unimaginable when I entered he field in the late 1960s.
5) What positive changes have you seen in the study of biology over your career? What challenges remain?
I have been gratified to see population genetics become much more important both in evolutionary biology and medical genetics. As one example, when I started in the field, linkage disequilibrium was an arcane and mathematically difficult subject that was thought to be of little or no practical importance. By the early 2000, patterns of linkage disequilibrium in the human genome motivated the multimillion dollar HapMap project which has evolutionized the study of inherited diseases.
6) If you could have dinner with any three biologists, who would they be?
I probably do not know enough about biology to benefit from dining with Charles Darwin, although I would like to ask him why he thought the theory of pengenesis was such a good idea. I would be too intimidated to dine with R. A. Fisher, although I would like to ask him why he carried on the feud with Sewall Wright. I would pick J. B. S. Haldane and H. J. Muller because of their immense breadth of knowledge and their creativity. I would still be intimidated but I would probably be able to swallow my food. For the third, I would pick
John Maynard Smith. Although I had many enjoyable dinners with him, they were not nearly enough.