My research in evolutionary genomics focuses on three major areas:
|In the study of speciation, a conundrum is how species can freely interbreed while being maintained
as distinct species. My research attempts to characterize genetic features
that contribute to speciation by preventing gene flow between species.
Specifically, I have examined 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).
As part of my doctoral research, together with collaborators, we used the classic model system for studying chromosomal inversions, Drosophila pseudoobscura and D. persimilis, performing one of the first population genomic studies using low-coverage whole-genome next generation sequencing to answer long standing evolutionary questions (see article). By comparing percent nucleotide divergence in three segregating inversions within- and between-species, we showed that the three inversions were segregating at the time of speciation, and that speciation occurred in geographic isolation for these species.
Later, I 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, I am 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, I am conducting a broad survey of various biological taxa with data appropriate for this type of analysis. This research project is part of a National Research Service Award through the NIH.
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. I am 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.
I am 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.
In my graduate and postdoctoral work, I have generated fine-scale genome-wide recombination maps in Drosophila persimilis (see article), Pan paniscus, Pan troglodytes ellioti, and Gorilla gorilla gorilla (Stevison et al. Submitted). For my doctoral work, I directly estimated recombination rates from high-throughput genotyping of a large-scale genetic cross using SNP markers developed from next-generation sequence data. For my postdoc, I indirectly estimated recombination rates using an linkage disequilibrium based approach with whole genome sequence data from 10-15 individuals each as part of the Great Ape Genome Project (see article). I found that the broad-scale correlation within species breaks down quickly despite very little change in sequence divergence between pairs. Additionally, I found 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. I 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 is currently in review (pre-print on BioRxiv) and has led to additional work on gorilla demography and selection (see article), and other works to be submitted this spring. I am also working on a recombination map for gibbons, examining rate variation outside of great apes.
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 my research, I have been involved in projects documenting the strength of introgression (gene flow) between hybridizing taxa. For my master's research, I published one of the first studies documenting sequence-based evidence at nuclear DNA of hybridization between the rhesus and cynomolgus macaque (see article).
More recently, as part of my postdoc, I have been involved in research comparing the relative contributions of neandertal DNA to different human populations, with the surprising conclusion that East Asians have higher levels of neandertal admixture compared to Europeans (see recent article). I am also working on multiple projects 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 recent article).