Open AccessIntensity of natural selection at the major histocompatibility complex loci.
Author(s) -
Yoko Satta,
Colm Ó'hUigín,
Naoyuki Takahata,
Jan Klein
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.15.7184
Subject(s) - nonsynonymous substitution , balancing selection , major histocompatibility complex , biology , selection (genetic algorithm) , natural selection , genetics , negative selection , gene , allele , neutral mutation , evolutionary biology , computational biology , machine learning , genome , computer science
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, KB, at the PBR and the mutation rate mu. We compared the five available methods for estimating KB 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.