Widespread purifying selection at polymorphic sites in human protein-coding loci

Austin L. Hughes, Bernice Packer, Robert Welch, Andrew W. Bergen, Stephen J. Chanock, Meredith Yeager

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Estimation of gene diversity (heterozygosity) at 1,442 single-nucleotide polymorphism (SNP) loci in an ethnically diverse sample of humans revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. This, in turn, suggests that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity even in a sample of modest size can help guide the search for disease-associated genes.

Original languageEnglish (US)
Pages (from-to)15754-15757
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Dec 23 2003
Externally publishedYes

ASJC Scopus subject areas

  • General


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