Genetic variation among extant individuals carries information about the evolutionary and genetic forces that have shaped their ancestors. Our research leverages this information to learn about recombination, demography and natural selection, in humans as well as in other species. To do so, we combine modeling, the development of statistical tools and data analysis; the lab is “dry”, although we often collaborate closely with experimentalists.

Below are examples of ongoing research projects:

Recombination in apes. The increasing availability of genomic resources enables us to address enduring questions about recombination, with important implications for human genetics and our understanding of adaptation. Current work focuses on (i) Characterizing the recombination landscape in humans (together with Graham Coop, Jonathan Pritchard and Carole Ober), (ii) Inferring the selective pressures acting on recombination by comparing recombination rates in humans and chimpanzees (with David Serre at McGill University), and (iii) Examining the relationship between recombination and adaptation in primates (with Graham Coop).

Recent publications in this area include Ptak et al. 2005 Nature Genetics and Coop and Przeworski 2007 Nature Genetics Reviews.

Generalizing models of selective sweeps. Considerable debate has focused on what proportion of genetic changes is favored by natural selection, as well as what types of substitutions are most likely to have been selected. To answer these questions, we need to be able to identify genomic regions that are or have been a target of selection. In other words, we need an accurate characterization of the effects of positive selection on patterns of genetic variability. Most of our current understanding stems from a simple model, in which a rare allele rapidly increases to fixation in a randomly mating population of constant size. However, for most organisms, there is evidence of departures from these demographic assumptions. Our research focuses on developing more general, and potentially more realistic, models of positive selection.

Cf. Przeworski et al. 2005 Evolution; Teshima et al. 2006 Genome Research.

Understanding local adaptations in humans (in collaboration with Anna Di Rienzo). A common interpretation of genome-wide selection scans is that the dispersal of anatomically modern humans from East Africa led to a number of recent adaptations. If so, patterns of polymorphism from non-African individuals should show the signature of adaptations dating to 40-100 Kya. To date, however, scans of polymorphism data from a limited number of populations have yielded conflicting results as to both the chronology and geography of local adaptations. To clarify these issues, we plan to use existing and new polymorphism data to infer a sensible demographic model for a large set of human populations. These models will provide a framework within which to characterize the timing and geographic distribution of adaptations in genes reported to have been under selection in one of three HapMap populations.

Estimating parameters of speciation models. Population divergence times are of interest in many contexts, from human genetics to conservation biology. These times can be estimated from multi-locus polymorphism data. However, existing approaches make a number of assumptions that limit their applicability. To overcome these limitations, we developed a new approach to estimate population parameters for a simple split model, allowing for migration as well as intralocus recombination. To illustrate its potential, we apply it to extensive polymorphism data from populations and species of apes, whose demographic histories are largely unknown.

Cf. Becquet et al. 2007 PLoS Genetics, Becquet and Przeworski 2007 Genome Research.