Abstract
Genome-wide scanning for signals of recent positive selection is essential for a comprehensive and systematic understanding of human adaptation. Here, we present a genomic survey of recent local selective sweeps, especially aimed at those nearly or recently completed. A novel approach was developed for such signals, based on contrasting the extended haplotype homozygosity (EHH) profiles between populations. We applied this method to the genome single nucleotide polymorphism (SNP) data of both the International HapMap Project and Perlegen Sciences, and detected widespread signals of recent local selection across the genome, consisting of both complete and partial sweeps. A challenging problem of genomic scans of recent positive selection is to clearly distinguish selection from neutral effects, given the high sensitivity of the test statistics to departures from neutral demographic assumptions and the lack of a single, accurate neutral model of human history. We therefore developed a new procedure that is robust across a wide range of demographic and ascertainment models, one that indicates that certain portions of the genome clearly depart from neutrality. Simulations of positive selection showed that our tests have high power towards strong selection sweeps that have undergone fixation. Gene ontology analysis of the candidate regions revealed several new functional groups that might help explain some important interpopulation differences in phenotypic traits.
Highlights
In approximately the past 50,000 years, anatomically modern human emerged from Africa and colonized most of the globe
Demonstrating conclusively that local selection has operated on a gene remains a difficult task because it involves several aspects: demonstrating that patterns of allelic variation at the gene are not consistent with neutrality; that there is a functional difference between alleles; and that the functional difference would result in a phenotypic effect that would be influenced by selection
We demonstrate that our method has greater power to detect selective sweeps that are fixed or nearly so, and we construct a statistical framework that shows that our method reliably detects positive selection
Summary
In approximately the past 50,000 years, anatomically modern human emerged from Africa and colonized most of the globe. Demonstrating conclusively that local selection has operated on a gene remains a difficult task because it involves several aspects: demonstrating that patterns of allelic variation at the gene are not consistent with neutrality; that there is a functional difference between alleles; and that the functional difference would result in a phenotypic effect that would be influenced by selection Such efforts have been mostly focused on individual candidate genes [6], and very few have had all these aspects demonstrated to some degree at least; examples of genes for which all these aspects have been shown include the lactose tolerance gene LCT [8], saltregulation genes at the CYP3A cluster [9], several disease resistance genes, e.g., G6PD and CASP12 [10,11], and pigmentation genes, e.g., SLC24A5 and MATP [12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
