Human Evolution and Archaic Hominin Gene Flow
Approximately 2% of the genome of each contemporary non-African human traces ancestry to ancient gene flow from Neanderthals. Preliminary evidence suggests that functional differences between modern human and Neanderthal-introgressed alleles influence variation in human traits and contribute to disease risk. Yet the mechanistic basis of these functional differences has remained poorly understood. My postdoctoral research in the Akey lab seeks to address this gap by leveraging RNA-seq and other genomic data from modern humans to reveal functional characteristics of Neanderthal-inherited alleles. This work has demonstrated that approximately one-quarter of persisting Neanderthal sequences exert measurable effects on human gene expression. See a video about our latest publication on this topic here: https://www.youtube.com/watch?v=xX2iv4SyNHg
Since my PhD, I have been collaborating with the prenatal genetic testing company Natera to investigate chromosome abnormalities affecting preimplantation human embryos. Gain or loss of whole chromosomes–a phenomenon called aneuploidy–is the leading cause of human pregnancy loss and congenital birth defects. By analyzing genomic data from more than 6,000 in vitro fertilization cycles and more than 40,000 embryos, my work has documented incidences and characteristics of diverse classes of aneuploidy with extreme resolution. Ongoing work with collaborators at Stanford and other institutions worldwide is shedding further light on the molecular basis of aneuploidy formation and factors influencing aneuploidy risk.
Genomic Resource Development
Much of my past research has focused on the development of high-quality genomic resources for non-model systems, thereby facilitating future molecular approaches to studying the ecology, evolution, and physiology of non-model species. Through collaboration with Illumina, I led a project to test the utility of TruSeq synthetic long-read technology (formerly Moleculo) for de novo genome assembly. Assembling the Drosophila melanogaster genome as a proof-of-concept, this work demonstrated that synthetic long-reads enable the accurate reconstruction and placement of highly repetitive transposable elements. This work has helped guide expectations for potential users as well as identify areas for future improvements. In a separate study, I developed an approach for simultaneous transcriptome assembly and single nucleotide polymorphism (SNP) marker discovery using multiplex RNA-seq. Applying this approach to an introduced population of the checkerspot butterfly Euphydryas gillettii, we demonstrated that demographic inference methods could accurately time a known historical bottleneck event. Photo credit: Carol Boggs.