My motivating scientific interest is in evolution. At root, evolution is a process of changing patterns of genetic variation. My research uses the tools of population genetics and genomics to investigate the rules that govern the generation, maintenance, distribution, fixation and elimination of genetic variants. I apply these tools in two overlapping model systems: transposable elements and human populations.
Transposable elements have several virtues as a model system, namely: (1) they are among the simplest natural replicating entities in existence; (2) they evolve in a context that is very different from that of other replicators, which allows us to probe the most fundamental and invariant features of evolution; (3) recent technological advances have made it possible to collect extensive and very detailed data sets on entire populations of transposons. These features allow us to generate population genetic models of the evolution of transposons and to test them with rich and diverse data sets.
The patterns of genetic variation in human populations are rapidly becoming extremely well-characterized. We have collected genotypic data from many individuals at many genetic markers of various kinds, then merged data sets collected by our laboratory and other labs to assemble a picture of human genetic variation across the entire genome and from around the world, at levels of detail ranging from continents to families. We then use these data sets to make inferences about the history of humans during the last million years or so, to improve our ability to identify phenotypically-relevant genetic variants, and to reconstruct the ancestry of individuals and groups.
Some of the genetic variants we study in humans and their primate relatives are the result of transposable elements, primarily of the Alu and L1 retrotransposon families. These variants play many roles: some of them are invaluable in reconstructing the history of primate evolution; others are useful as markers of demographic events in human history; many have altered the structure of the human genome; and some have become the raw material of phenotypic evolution by altering or creating new gene functions.
My research is concentrated on the study human evolution and disease through the analysis of patterns of genetic diversity. I employ a variety of statistical and computational approaches, drawing heavily from the population genetics and statistical genetics literature. My current projects include fine-scale mapping of Crohn’s disease mutations using an evolutionary perspective, analysis of full-genome sequence data from a family with a history of a rare disease, and theoretical modeling to explain ancient genealogies associated with rare mobile element polymorphisms. Other recent projects include the detection of recent positive selection across the genome in various human populations, and the development of methods to analyze ancient autosomal Neanderthal DNA that has been contaminated by modern humans. I am particularly interested in scenarios that involve recent human evolution and that have resulted in genetic differences in disease susceptibility both within and between populations, and in the future I expect this to be a major focus of my research.