Research

Our research in evolutionary genomics focuses on three major areas:

Speciation genetics

In the study of speciation, a conundrum is how species can freely interbreed while being maintained as distinct species. Our research attempts to characterize genetic features that contribute to speciation by preventing gene flow between species. Specifically, the Stevison lab is interested in the role of chromosomal inversions to restrict recombination between species, contributing to higher rates of nucleotide divergence (see graphic on right for representation of this process). Together with collaborators, Dr. Stevison performed one of the first population genomic studies using low-coverage whole-genome next generation sequencing for part of her dissertation to answer long standing evolutionary questions in the classic model system for studying chromosomal inversions,Drosophila pseudoobscura and D. persimilis (see article. By comparing percent nucleotide divergence in three segregating inversions within- and between-species, our work showed that the three inversions were segregating at the time of speciation, and that speciation occurred in geographic isolation for these species.

Later, we performed additional work in this system which confirmed that inversions also disrupt recombination rates throughout the genome (not just inside inversions), and that these disruptions correlate with levels of interspecies nucleotide divergence. This was the first study to examine how enhanced, rather than inhibited, recombination rates contribute to variation in interspecies divergence (see article). To follow-up on this exciting result, we are now working to quantify recombination rate differences in hybrids relative to intraspecies genetic maps, and examine whether these differences correlate with variation in nucleotide divergence between species. To determine the universality of this putative pattern and to identify novel genetic features important in speciation, we are conducting a broad survey of various biological taxa with data appropriate for this type of analysis. 

Recently, we have become interested in how complex genetic variants, such as structural variants can influence variation in gene flow and act as barriers to reproduction in a similar manner as chromosomal inversions. We are using novel methods to detect complex genetic variants in whole genome sequence data.

Recombination rate evolution and its impact on genomic architecture

Recombination occurs when chromosomes exchange genetic material when being put into gametes, which is the main reason why no two offspring from the same set of parents look exactly alike. Our lab is interested in quantifying the amount of variability in recombination rate and understanding how selection and/or mutation drive ubiquitous correlations between nucleotide diversity/divergence and GC-content. We are also interested in the evolution of hotspot sharing across taxa. Typically, hotspots evolve very rapidly within and between species, whereas broad-scale rates (~1 Megabase) tend to show tight correlations between species. While recombination rates are free to evolve in different directions as species evolve, the tight regulation of recombination may limit how much rates can change both mechanistically and evolutionarily.

Work from our lab generated fine-scale genome-wide recombination maps in Drosophila persimilis (see article), Pan paniscus, Pan troglodytes ellioti, and Gorilla gorilla gorilla (see article), the latter was part of the Great Ape Genome Project (see article). Work in our lab uses two major approaches to estimating recombination rates - (a) direct from high-throughput genotyping of large-scale genetic crosss using SNP markers developed from next-generation sequence data and (b) indirect using an linkage disequilibrium based approach with using population genomic sequence data from 10-15 individuals. Our work on great apes showed that the transcription factor PRDM9, previously shown to localize to human recombination hotspots, explains variation in recombination rates at hotspots more broadly across great apes. We attribute the previously reported lack of signal in western chimp to higher allelic variation at PRDM9 in the Pan genus and lower quality at fine-scales for rate estimates for previous work. This work has led to additional work on gorilla demography and selection (see article), and other works currently ongoing. We are also working on a recombination map for gibbons and baboons, examining rate variation outside of great apes.

Additionally, our work found that the broad-scale correlation within species breaks down quickly despite very little change in sequence divergence between pairs. We attribute this rapid change in recombination rate to environmental induced changes in recombination, known for nearly a century as 'plasticity' in recombination rates. To understand the role of the environment on recombination, our lab continues to work with the model species Drosophila pseudoobscura.

Variation in levels of introgression across the genome

The discovery of a non-uniform distribution of hybridization across the genome has transformed the way we think about the process of speciation and our understanding of how species are maintained despite hybridization. In our lab, we are interested in projects documenting the strength of introgression (gene flow) between hybridizing taxa. Previous work in this area includes work on macaques. Dr. Stevison published one of the first studies documenting sequence-based evidence at nuclear DNA of hybridization between the rhesus and cynomolgus macaque (see article).

Previous work in this area includes research comparing the relative contributions of neandertal DNA to different human populations, with the surprising finding East Asians to have higher levels of neandertal admixture compared to Europeans (see article). We also previously worked in collaboration with Dr. Nadav Ahituv at UCSF to characterize nucleotide changes along the human/neandertal lineage resulting in corresponding changes in enhancer function during neural development (see article).