UCSF

Human accelerated regions (HARS), which are genome sequences that have evolved at an accelerated rate in the human lineage, have previously been shown to include developmental enhancers. I have used a massively parallel enhancer reporter assay (MPRA) to test a library of human and chimp HAR orthologs in a cell model of mammalian testes, in order to find HARS which have evolved in human and may underly unique human reproductive traits. Through luciferase assay, 4C-seq, transcriptional analysis and Crispr/Cas9 deletion I have validated a candidate and shown that it is an enhancer of the hedgehog signaling pathway effector Gli2 in the testis cell model. Furthermore, I have shown that the enhancer is required for normal Gli2 expression in Leydig cells, as well as normal testis vascular development and normal inter-male social behavior.