Clusters of adaptive evolution in the human genome

Laura Scheinfeldt

doi:10.3389/fgene.2011.00050

Abstract

Considerable work has been devoted to identifying regions of the human genome that have been subjected to recent positive selection. Although detailed follow-up studies of putatively selected regions are critical for a deeper understanding of human evolutionary history, such studies have received comparably less attention. Recently, we have shown that ALMS1 has been the target of recent positive selection acting on standing variation in Eurasian populations. Here, we describe a careful follow-up analysis of genetic variation across the ALMS1 region, which unexpectedly revealed a cluster of substrates of positive selection. Specifically, through the analysis of SNP data from the HapMap and Human Genome Diversity Project–Centre d’Etude du Polymorphisme Humain samples as well sequence data from the region, we find compelling evidence for three independent and distinct signals of recent positive selection across this 3 Mb region surrounding ALMS1. Moreover, we analyzed the HapMap data to identify other putative clusters of independent selective events and conservatively discovered 19 additional clusters of adaptive evolution. This work has important implications for the interpretation of genome-scans for positive selection in humans and more broadly contributes to a better understanding of how recent positive selection has shaped genetic variation across the human genome.

Highlights

Interest in identifying regions of the human genome that have been subjected to recent positive selection has grown considerably since the availability of whole genome SNP and sequence data, resulting in large lists of candidate selection genes (Akey, 2009)
We described a detailed analysis of the evolutionary history of ALMS1 variation, which has a strong signature of selection from standing variation in European and Asian populations (Scheinfeldt et al, 2009)
The observation of finding clusters of highly differentiated. What emerges from this analysis is a striking incidence of multiple, independent, and regionally restricted signals of positive selection in a 3-MB region on chromosome 2

Summary

Introduction

Interest in identifying regions of the human genome that have been subjected to recent positive selection has grown considerably since the availability of whole genome SNP and sequence data, resulting in large lists of candidate selection genes (Akey, 2009). We described a detailed analysis of the evolutionary history of ALMS1 variation, which has a strong signature of selection from standing variation in European and Asian populations (Scheinfeldt et al, 2009). We focus on a detailed analysis of a 3-Mb region encompassing ALMS1 that possesses patterns of variation consistent with the action of three independent selective events in human history. Several of the clusters we identified contain previously known candidate genes for selection; these regions have been interpreted as a single signature of selection across linked loci and possible independent selective events were not considered. Follow-up studies of genes and regions identified in genome-wide scans for positive selection are critical to foster a deeper understanding of the mechanistic basis of recent human evolutionary history

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Conclusion