Clusters of Adaptive Evolution in the Human Genome

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

Population Genomics of Intron Splicing in 38 Saccharomyces cerevisiae Genome Sequences

Introns are a ubiquitous feature of eukaryotic genomes, and the dynamics of intron evolution between species has been extensively studied. However, comparatively few analyses have focused on the evolutionary forces shaping patterns of intron variation within species. To better understand the population genetic characteristics of introns, we performed an extensive population genetics analysis on key intron splice sequences obtained from 38 strains of Saccharomyces cerevisiae. As expected, we found that purifying selection is the dominant force governing intron splice sequence evolution in yeast, formally confirming that intron-containing alleles are a mutational liability. In addition, through extensive coalescent simulations, we obtain quantitative estimates of the strength of purifying selection (2Nes ≈ 19) and use diffusion approximations to provide insights into the evolutionary dynamics and sojourn times of newly arising splice sequence mutations in natural yeast populations. In contrast to previous functional studies, evolutionary analyses comparing the prevalence of introns in essential and nonessential genes suggest that introns in nonribosomal protein genes are functionally important and tend to be actively maintained in natural populations of S. cerevisiae. Finally, we demonstrate that heritable variation in splicing efficiency is common in intron-containing genes with splice sequence polymorphisms. More generally, our study highlights the advantages of population genomics analyses for exploring the forces that have generated extant patterns of genome variation and for illuminating basic biological processes