UCSF Institute for Human Genetics

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Duke University

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Research

My 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. 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 and article on this topic).

As part of my doctoral research, I 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. Mechanistically, recombination is necessary to stabilize chromosomes during meiosis, but too many recombination events can lead to birth defects/disease. Evolutionarily, recombination helps to shuffle beneficial alleles onto common genetic backgrounds, facilitating the efficacy of selection, but too much recombination can break down these associations. 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.

As part of my PhD, I was involved in building a recombination map based on genotype data in genetic crosses within Drosophila persimilis (see article). Currently, I am building genetic maps based on linkage disequilibrium between single nucleotide polymorphisms (SNPs) using whole genome sequence data in various great apes and other primates. Specifically, I am working to to build genetic maps for chimps, bonobos and gorillas as part of the Great Ape Genome Diversity consortium (See talk on these results). Having additional comparisons of fine-scale recombination rate variation among primates will help us examine how nucleotide divergence predicts the amount of hotspot sharing within and between species (See recent talk on this topic).

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).