A Practical Genome Scan for Population-Specific Strong Selective Sweeps That Have Reached Fixation

Ryosuke Kimura,Akihiro Fujimoto,Katsushi Tokunaga,Jun Ohashi,Henry Harpending

doi:10.1371/journal.pone.0000286

Ryosuke Kimura, Akihiro Fujimoto + Show 3 more

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https://doi.org/10.1371/journal.pone.0000286

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Abstract

Phenotypic divergences between modern human populations have developed as a result of genetic adaptation to local environments over the past 100,000 years. To identify genes involved in population-specific phenotypes, it is necessary to detect signatures of recent positive selection in the human genome. Although detection of elongated linkage disequilibrium (LD) has been a powerful tool in the field of evolutionary genetics, current LD-based approaches are not applicable to already fixed loci. Here, we report a method of scanning for population-specific strong selective sweeps that have reached fixation. In this method, genome-wide SNP data is used to analyze differences in the haplotype frequency, nucleotide diversity, and LD between populations, using the ratio of haplotype homozygosity between populations. To estimate the detection power of the statistics used in this study, we performed computer simulations and found that these tests are relatively robust against the density of typed SNPs and demographic parameters if the advantageous allele has reached fixation. Therefore, we could determine the threshold for maintaining high detection power, regardless of SNP density and demographic history. When this method was applied to the HapMap data, it was able to identify the candidates of population-specific strong selective sweeps more efficiently than the outlier approach that depends on the empirical distribution. This study, confirming strong positive selection on genes previously reported to be associated with specific phenotypes, also identifies other candidates that are likely to contribute to phenotypic differences between human populations.

Highlights

Modern human populations exhibit large phenotypic differences in morphological and physiological traits such as pigmentation, hair shape, body shape and composition, and enzymatic activities
The SNPs were placed at intervals of 2 kb and the center SNP (51st) was regarded as the selected polymorphism
Individual chromosomes of the founder generation at the population split (G = 0) were numbered, and the state of chromosomes at each generation was denoted by this number, not by allelic state

Summary

Introduction

Modern human populations exhibit large phenotypic differences in morphological and physiological traits such as pigmentation, hair shape, body shape and composition, and enzymatic activities. Such phenotypic divergences between populations are considered to result from genetic adaptation to local environments; people have experienced changes in their environment due to migration and establishment of civilizations over the past 100,000 years. To detect recent hitchhiking events, one practical approach is to search for genetic regions that have undergone few previous recombination events [2] Another selection clue is high local genetic differentiation that can be measured with FST [3] when at least two populations are examined. To detect loci that have reached fixation, low nucleotide diversity should be considered along with the aforementioned points

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