Using exome sequencing to study adaptive evolution in non-human primates and human populations

Abstract

Positive selection promotes the fixation of functional genetic differences. Studying these adaptive differences can provide insights into how species adapt to their environment and develop their unique phenotypes. In this dissertation, I explore the effects of positive selection on the evolution of modern humans and non-human primates. I first describe current methods to detect positive selection and review how advances in next-generation sequencing technologies have improved our ability to detect adaptive events. I then present the first application of whole exome sequencing to non-human primates and describe new bioinformatic methods to assemble protein coding sequences for species without reference genomes. Using these coding sequences I scan the primate genome for genes experiencing positive selection and identify a novel class of adaptively evolving genes involved in keratinization. I then examine the effect of recurrent positive selection acting both in non-human primates and human populations using a large human exome data set from the NHLBI’s Exome Sequencing Project. I find that genes with evidence for long-term positive selection in non-human primates also show diversity patterns in humans that are consistent with continued positive selection. I conclude by discussing the trade-offs between whole-genome and exome sequencing, the need for more quality reference genomes and the difficulties in distinguishing adaptive evolution from other non-selective biological processes.