Intensity of natural selection at the major histocompatibility complex loci

Yoko Satta, Colm O'Huigin, Naoyuki Takahata, Jan Klein

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135 Scopus citations

Abstract

Long persistence of allelic lineages, prevalence of nonsynonymous over synonymous substitutions in the peptide-binding region (PBR), and deviation from neutrality of the expected gene identity parameter F all indicate indirectly that balancing selection is operating at functional major histocompatibility complex (MHC) loci. Direct demonstrations of the existence of balancing selection at MHC loci are, however, either lacking or not fully convincing. To define the conditions under which balancing selection could be demonstrated, we estimated its intensity from the mean number of nonsynonymous substitutions, K(B), at the PBR and the mutation rate μ. We compared the five available methods for estimating K(B) by computer simulation and chose the most reliable ones for estimation of selection intensity. For the human MHC, the selection coefficients of the HLA-A, -B, - C, -DRB1, -DQB1, -DQA1, and -DPB1 loci are 0.015, 0.042, 0.0026, 0.019, 0.0085, 0.0028, and 0.0007, respectively. This low selection intensity places severe restrictions on the possibility of measuring selection directly in vertebrate populations.

Original languageEnglish (US)
Pages (from-to)7184-7188
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number15
DOIs
StatePublished - Jul 19 1994

All Science Journal Classification (ASJC) codes

  • General

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