Abstract

Among the many morphological changes that took place during human origins, an expansion in brain volume is particularly conspicuous. My group is using computational and functional genomic approaches to identify candidate loci underlying human-specific features of brain anatomy in conjunction with mouse models and induced pluripotent stem cells to validate and understand the phenotypic consequences of mutations within those loci. We discovered an enhancer containing human lineage-specific mutations that drive elevated expression of the Wnt receptor FZD8 within neural progenitor cells during early corticogenesis, decreasing their cell cycle time, and increasing cell number and overall brain volume. We have also identified changes in lipid metabolism in adipocytes that result in increased production of diacylglycerides, which we hypothesize are essential for the greatly expanded surface area of neural- and glial cell membranes in the human brain.

Prof. Gregory A. Wray – Personal Statement

My overarching research goal is to understand the evolution of the genotype-phenotype relationship. My group uses a combination of empirical and computational approaches to identify functional variants that alter gene expression, to identify the underlying molecular mechanisms, and to understand their trait consequences. I have considerable experience using genome-wide analyses of population variation and between-species comparisons to identify functional variants within cis-regulatory regions that affect transcript abundance and chromatin configuration. My group was the first to carry out DNase-seq analyses to identify human-specific evolutionary gains and losses of active regulatory elements and among the first to carry out RNA -seq analyses to identify gene expression differences between humans and nonhuman primates. My group was also among the first to develop and apply methods to test for signatures of positive selection in noncoding DNA throughout the genomes of great apes. Although my experience studying malaria is limited, the experimental and analytical methods from my work on human evolution prepare me well for this project.