Positive selection in the human lineage across time scales

Abstract

Understanding the evolutionary history of humankind has long been a central goal of biology. This history extends over millions of years- beginning with the events that led to our divergence from chimpanzees and other primate relatives, and ending with the ongoing migration patterns that give rise to the diverse human populations we see today. DNA sequencing and other molecular techniques for ascertaining genetic variation have been instrumental in reconstructing the timeline of this history. However, these technologies can also be leveraged to answer more fundamental questions about the ways that natural selection has shaped human evolution. For instance, studying patterns of DNA variation can elucidate the genetic basis of traits that were selected for in the human lineage across time scales. Although many methods have been developed to identify these signatures that natural selection has left on our genomes, there are still many cases of positive selection that current methods are not designed to detect. Here I present novel genome-wide approaches for detecting natural selection at two different points in human history. In the first, I extended methods to identify regulatory elements that show elevated rates of human-specific substitutions, and may thus underlie unique human phenotypes that evolved after our divergence from other apes. In the second, I characterized haplotypes inherited from interbreeding events with archaic hominin species that facilitated modern human adaptation to out of Africa environments. Both of these approaches build significantly on previous work to identify positive selection in the human genome, and provide an extensive catalogue of loci to study using more targeted hypotheses in the future.