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Communicated by Douglas C. Wallace, University of California, Irvine, CA, November 9, 2005 (received for review June 8, 2005)
Abstract
By using the 1.6 million single-nucleotide polymorphism (SNP) genotype data set from Perlegen Sciences [Hinds, D. A., Stuve, L. L., Nilsen, G. B., Halperin, E., Eskin, E., Ballinger, D. G., Frazer, K. A. & Cox, D. R. (2005) Science 307, 1072–1079], a probabilistic search for the landscape exhibited by positive Darwinian selection was conducted. By sorting each high-frequency allele by homozygosity, we search for the expected decay of adjacent SNP linkage disequilibrium (LD) at recently selected alleles, eliminating the need for inferring haplotype. We designate this approach the LD decay (LDD) test. By these criteria, 1.6% of Perlegen SNPs were found to exhibit the genetic architecture of selection. These results were confirmed on an independently generated data set of 1.0 million SNP genotypes (International Human Haplotype Map Phase I freeze). Simulation studies indicate that the LDD test, at the megabase scale used, effectively distinguishes selection from other causes of extensive LD, such as inversions, population bottlenecks, and admixture. The ≈1,800 genes identified by the LDD test were clustered according to Gene Ontology (GO) categories. Based on overrepresentation analysis, several predominant biological themes are common in these selected alleles, including host–pathogen interactions, reproduction, DNA metabolism/cell cycle, protein metabolism, and neuronal function.
Footnotes
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↵ § To whom correspondence should be addressed. E-mail: rmoyzis{at}uci.edu.
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Author contributions: E.T.W., G.K., P.B., and R.K.M. designed research; E.T.W. performed research; E.T.W., P.B., and R.K.M. contributed new reagents/analytic tools; E.T.W. and R.K.M. analyzed data; and E.T.W., P.B., and R.K.M. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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Abbreviations: ALnLH, average log likelihood; CEU, European ancestry; CHB, Han Chinese ancestry; FRC, fraction of inferred recombinant chromosomes; GO, Gene Ontology; HapMap, International Haplotype Map; JPT, Japanese ancestry; LD, linkage disequilibrium; LDD, LD decay; SNP, single-nucleotide polymorphism; YRI, African (Yoruba) ancestry.
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Freely available online through the PNAS open access option.
- Copyright © 2006, The National Academy of Sciences
Global landscape of recent inferred Darwinian selection for Homo sapiens
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