Adaptive evolution: From genome-wide scans to biological significance.

摘要

To understand the functional relevance of a single adaptive mutation it is necessary to identify the region under positive selection, then narrow down the region to the adaptively evolving gene and single nucleotide polymorphism, and characterize how the mutation alters the gene function. In this dissertation I describe two large-scale scans designed to identify adaptively evolving loci followed by in-depth study of one of these loci. One method to identify adaptively evolving loci is to scan the available data for signatures of positive selection, for example by testing for elevated dN/d S ratios. Using dN/dS ratios to identify specific amino acid sites that have been subject to positive selection, it is possible to identify potential functionally important amino acid changes. In a study of Caenorhabditis elegans and C. briggsae chemoreceptors, I identified the SRZ chemoreceptor gene family to be adaptively evolving. In addition to using dN/dS ratios, analysis of population level variation is used to predict adaptively evolving loci. However, it is much more difficult to pinpoint the specific adaptive mutation using population level variation, due to the confounding effects of hitchhiking and demography. Once a locus, or several loci, has been identified, it is important to characterize the evolutionary history of the locus in order to understand the biological relevance of the selected allele. In a genome-wide scan for adaptive evolution in three human populations described in this dissertation 385 loci were identified as candidate selection genes. I characterized the evolutionary history of one such locus, enamelin, in ten human populations and twelve primate species. enarnelin is a gene involved in tooth enamel formation. In addition to detecting population-specific evidence for positive selection, I found a correlation between diet changes and bursts of adaptive evolution in enamelin. These findings suggest that adaptive evolution in enamelin is related to dietary shifts. Identification of the functional relevance of predicted adaptive changes is one of the greatest challenges presented by studying adaptive evolution.