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PMID: 19737746 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Population differentiation as an indicator of recent positive selection in humans: an empirical evaluation.

Genetics ·Vol. 183 ·No. 3 ·2009-11-00 ·Pages 1065-77

Xue Y, Zhang X, Huang N, Daly A, Gillson CJ, Macarthur DG, Yngvadottir B, Nica AC, Woodwark C, Chen Y, Conrad DF, Ayub Q, Mehdi SQ, Li P, Tyler-Smith C

Abstract

We have evaluated the extent to which SNPs identified by genomewide surveys as showing unusually high levels of population differentiation in humans have experienced recent positive selection, starting from a set of 32 nonsynonymous SNPs in 27 genes highlighted by the HapMap1 project. These SNPs were genotyped again in the HapMap samples and in the Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) panel of 52 populations representing worldwide diversity; extended haplotype homozygosity was investigated around all of them, and full resequence data were examined for 9 genes (5 from public sources and 4 from new data sets). For 7 of the genes, genotyping errors were responsible for an artifactual signal of high population differentiation and for 2, the population differentiation did not exceed our significance threshold. For the 18 genes with confirmed high population differentiation, 3 showed evidence of positive selection as measured by unusually extended haplotypes within a population, and 7 more did in between-population analyses. The 9 genes with resequence data included 7 with high population differentiation, and 5 showed evidence of positive selection on the haplotype carrying the nonsynonymous SNP from skewed allele frequency spectra; in addition, 2 showed evidence of positive selection on unrelated haplotypes. Thus, in humans, high population differentiation is (apart from technical artifacts) an effective way of enriching for recently selected genes, but is not an infallible pointer to recent positive selection supported by other lines of evidence.

MeSH Terms
Alcohol Dehydrogenase/genetics Antigens, CD/genetics Cell Adhesion Molecules/genetics DNA Helicases/genetics DNA Repair Enzymes/genetics Duffy Blood-Group System/genetics Edar Receptor/genetics Gene Frequency Genetic Variation Genetics, Population Genome, Human/genetics Genotype Guanine Nucleotide Exchange Factors/genetics Haplotypes/genetics Humans Intracellular Signaling Peptides and Proteins/genetics Poly-ADP-Ribose Binding Proteins Polymorphism, Single Nucleotide/genetics Receptors, Cell Surface/genetics Selection, Genetic Sequence Analysis, DNA Ubiquitin-Protein Ligases
Chemicals
ACKR1 protein, human Antigens, CD CD66 antigens Cell Adhesion Molecules Duffy Blood-Group System EDAR protein, human Edar Receptor GNB1L protein, human Guanine Nucleotide Exchange Factors Intracellular Signaling Peptides and Proteins Poly-ADP-Ribose Binding Proteins Receptors, Cell Surface ADH1B protein, human Alcohol Dehydrogenase HERC1 protein, human Ubiquitin-Protein Ligases DNA Helicases ERCC6 protein, human DNA Repair Enzymes
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Xue Yali
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, United Kingdom.
Zhang Xuelong
Huang Ni
Daly Allan
Gillson Christopher J
Macarthur Daniel G
Yngvadottir Bryndis
Nica Alexandra C
Woodwark Cara
Chen Yuan
Conrad Donald F
Ayub Qasim
Mehdi S Qasim
Li Pu
Tyler-Smith Chris
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
1943-2631
DOI
10.1534/genetics.109.107722
Published
2009-11-00
Epub
2009-00-07
Pages
1065-77
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC2778960
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1534/genetics.109.107722 PMC Full Text View journal details
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