Biology Department

Research Overview

Presgraves Lab Website

I am interested in the evolutionary genetics of speciation and in adaptation at the molecular level. In particular, I'd like to know: what types of molecular changes distinguish the genomes of closely related species? And what population genetic forces govern the evolution of these changes? To get at these questions, I focus on the genetics of speciation and species differences in Drosophila and, more recently, I have turned to genomic data to test population genetic theory concerning the evolutionary advantages of recombination.

Speciation Genetics

Speciation occurs as reproductive barriers--like the intrinsic sterility or inviability of hybrids--evolve between populations. The fitness problems suffered by species hybrids stem from incompatible genetic interactions: newly evolved genes that function well in one species are sometimes functionally incompatible with interacting genes from other species. I am interested in how coevolution among interacting molecules within each species can drive the evolution of incompatible interactions between them. At the moment only a handful of genes involved in such hybrid incompatibilities are known. Therefore, one of the major goals of the lab is to identify a large number of these "speciation genes", and their interacting molecules, so we can begin to infer generalities about their identities, functions, and evolutionary histories.

By taking advantage of the genetic trickery available in D. melanogaster, I have identified twenty small regions scattered throughout the D. simulans autosomal genome that cause lethality when combined with the D. melanogaster X. So far I have narrowed the cause of hybrid lethality down to a single locus in each of three regions. One of these encodes the nuclear pore protein, Nup96. This comes as a surprise because the structures and functions of nuclear pore proteins are highly evolutionarily conserved among eukaryotes from yeast to humans. Nevertheless, our population genetic analyses show that positive natural selection drove the evolution Nup96 in both the D. melanogaster and D. simluans lineages in just the last few million years.

The Nup96 protein is embedded in a network of interacting proteins in the nuclear pore. I have therefore begun testing if the recent functional divergence of Nup96 exerts pressure on its interacting proteins to evolve compensatory substitutions. Several of these proteins show clear signs adaptive coevolution--including the sole interactor located on the X chromosome. In future work, we will use transgenic experiments to functionally test if this X-linked gene is the partner in the Nup96 hybrid incompatibility. Several other projects aimed at identifying speciation genes are also underway including among the younger species of the D. simulans clade.

Testing population genetics theory of linkage and selection

Population genetic theory predicts that sexual recombination increases the efficacy of natural selection. Selection acting on variation at one site in the genome can interfere with selection at tightly linked sites. By removing the effects of such interference, recombination facilitates the elimination of deleterious mutations and the fixation of beneficial ones. My collaborator, Andrea Betancourt, and I have performed several tests of this theory using genomic data from Drosophila.

In one test, we take advantage of the fact that different regions of the Drosophila genome experience different rates of recombination: we showed that genes located in regions with higher recombination rates are freer to respond to directional selection than those located in regions of lower recombination. In another test, we take advantage of the fact that the average strength of selection acting on synonymous mutations is weaker than that acting on amino acid changing nonsynonymous ones: we showed that the efficacy of weak selection for "preferred" synonymous codons (those thought to increase the speed and accuracy of translation) is compromised when repeated bouts of strongly selected nonsynonymous substitution occur at nearby sites.

I am expanding work in this area, including analyses of polymorphism data and of increasingly abundant genomic data from other organisms.