Graduate Programs in the Life Sciences

Research Focus

My research is focused on four major areas:

Population genetic theory- My primary research focuses on developing statistical methods for parameter estimation and hypothesis testing in population genetics and molecular phylogenetics. I am particularly interested in developing methods for estimating the relative contributions of demographic forces (e.g., population structure, population size expansion / contraction) and selective forces on the history of natural populations using data from standing genetic variation as well fixed differences between populations.

Human population genetics- The completion of the human, chimpanzee, and macaque genomes coupled with large-scale experiments to document human genetic variation provide us an unprecedented opportunity to study the evolution of our species. In collaboration with Andy Clark and Rasmus Nielsen, our group has been developing novel tools to facilitate this study as well as applying the tools to novel and interesting data sets. For example, as a joint effort between our three groups, we recently completed the first genome-wide comparison of human genetic variation within protein-coding genes to the genetic differences between humans and chimpanzees (Bustamante et al., 2005; Nature 437:1153-7)

Evolutionary genomics of domestication- Ever since Darwin, evolutionary biologists have sought to use human-driven evolutionary change as a model for understanding organic evolution. Some of the most profound and rapid changes in character evolution have been driven by farmers, enthusiasts, and plant and animal breeders using artificial selection to modify the phenotypes of hundreds of domesticated species. This type of intense and focused selection has invariably altered the genomes of domesticated species, affording us both an opportunity for understanding patterns of genetic variation in species subject to intense selection as well as the raw material from population samples for identifying genes of large phenotypic effect. As part of this work, we are analyzing large scale genetic variation data from diferent domesticated plant and animal species including the domestic dog and rice.

Association mapping in natural populations- The ease of rapid genotyping coupled with massive phenotyping (such as measuring gene expression simultaneously across tens of thousands of gene) presents an exiting challenge for evolutionary statistical genomics. By developing and deploying tools for linking genetic variation with agronomic or medical phenotypes of interest, my group hopes to help experimental geneticists identify genomic regions, genes, and specific mutations underlying complex traits. Several statistical problems that arise in this endeavor include: detecting cryptic population structure in samples of cases and controls, multiple testing from scanning many markers and many phenotypes, and disentangling correlations due to shared regulatory networks of co-regulated genes.