INTENSITY OF NATURAL-SELECTION AT THE MAJOR HISTOCOMPATIBILITY COMPLEX LOCI
INTENSITY OF NATURAL-SELECTION AT THE MAJOR HISTOCOMPATIBILITY COMPLEX LOCI
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DOI：
10.1073/pnas.91.15.7184
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发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
KLEIN, J
中科院分区：
文献类型：
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作者：
SATTA, Y;OHUIGIN, C;KLEIN, J
等位基因谱系的长期存在，多肽结合区(PBR)非同义取代的盛行，以及预期基因同一性参数F偏离中性，这些都间接地表明，平衡选择是在功能性主要组织相容性复合体(MHC)基因座上进行的。然而，MHC基因座存在平衡选择的直接证据要么缺乏，要么不完全令人信服。为了确定平衡选择的条件，我们根据PBR时非同义替换的平均数量K-B和突变率u来估计平衡选择的强度。通过计算机模拟比较了5种常用的K-B估计方法，选出了最可靠的选择强度估计方法。人类MHC中，A、B、C、DRB1、-DQA1、-DQA1和-DPB1基因座的选择系数分别为0.015、0.042、0.0026、0.019、0.0085、0.0028和0.0007。这种低选择强度严重限制了在脊椎动物种群中直接测量选择的可能性。
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.