INTENSITY OF NATURAL-SELECTION AT THE MAJOR HISTOCOMPATIBILITY COMPLEX LOCI

被引:143
作者
SATTA, Y
OHUIGIN, C
TAKAHATA, N
KLEIN, J
机构
[1] GRAD UNIV ADV STUDIES, DEPT GENET, MISHIMA, SHIZUOKA 411, JAPAN
[2] UNIV MIAMI, SCH MED, DEPT MICROBIOL & IMMUNOL, MIAMI, FL 33101 USA
关键词
D O I
10.1073/pnas.91.15.7184
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 mu. 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.
引用
收藏
页码:7184 / 7188
页数:5
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