A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes
A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes
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DOI：
10.1073/pnas.1031592100
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发表时间：
2003-07-22
影响因子：
11.1
通讯作者：
Innan, H
中科院分区：
文献类型：
--
作者：
Innan, H
建立了一个具有选择的双位点基因转换模型。在选择、突变、基因转换、重组和随机遗传漂变的共同作用下，采用扩散方法，在较强选择的假设下，得到了等位基因频率矩的期望值和两个基因座内和两个基因座间的期望变异量的近似公式。结果表明，等位基因变异的模式主要是由基因转换和选择之间的平衡，因为这两种机制在相反的方向上发挥作用。作为理论结果的一个应用，考虑了人类RHCE和RHD基因。仅在外显子7周围的短区域中观察到两个基因之间非常高水平的氨基酸差异。已知外显子7编码表征RHCE和RHD抗原之间差异的氨基酸。观察到的DNA变异在这个区域的模式是一致的选择模型在这篇文章中开发的，这表明强选择可能是工作，以保持RHCE/RHD抗原变异的两个位点系统。根据理论结果估计了选择强度。
A two-locus gene conversion model with selection is developed. Under the joint action of selection, mutation, gene conversion, recombination, and random genetic drift, approximate formulas for the expectations of the moments of allele frequencies and the expected amounts of variation within and between two loci are obtained by a diffusion method assuming relatively strong selection. It is shown that the pattern of allelic variation is mainly determined by the balance between gene conversion and selection, because these two mechanisms act in opposite directions. As an application of the theoretical results, the human RHCE and RHD genes are considered. The very high level of amino acid divergence between the two genes is observed only in a short region around exon 7. It is known that exon 7 encodes amino acids that characterize the difference between the RHCE and RHD antigens. The observed pattern of DNA variation in this region is consistent with the selection model developed in this article, suggesting that strong selection might be working to maintain the RHCE/RHD antigen variation in the two-locus system. The selection intensity is estimated on the basis of the theoretical result.