Hedrick Philip W
Department of Biology, Arizona State University, Tempe 85287, USA.
Evolution. 2002 Oct;56(10):1902-8. doi: 10.1111/j.0014-3820.2002.tb00116.x.
Balancing selection in the form of heterozygote advantage, frequency-dependent selection, or selection that varies in time and/or space, has been proposed to explain the high variation at major histocompatibility complex (MHC) genes. Here the effect of variation of the presence and absence of pathogens over time on genetic variation at multiallelic loci is examined. In the basic model, resistance to each pathogen is conferred by a given allele, and this allele is assumed to be dominant. Given that s is the selective disadvantage for homozygotes (and heterozygotes) without the resistance allele and the proportion of generations, which a pathogen is present, is e, fitnesses for homozygotes become (1 - s)((n - 1)e) and the fitnesses for heterozygotes become (1 - s)((n - 2)e), where n is the number of alleles. In this situation, the conditions for a stable, multiallelic polymorphism are met even though there is no intrinsic heterozygote advantage. The distribution of allele frequencies and consequently heterozygosity are a function of the autocorrelation of the presence of the pathogen in subsequent generations. When there is a positive autocorrelation over generations, the observed heterozygosity is reduced. In addition, the effects of lower levels of selection and dominance and the influence of genetic drift were examined. These effects were compared to the observed heterozygosity for two MHC genes in several South American Indian samples. Overall, resistance conferred by specific alleles to temporally variable pathogens may contribute to the observed polymorphism at MHC genes and other similar host defense loci.
有人提出，以杂合子优势、频率依赖选择或随时间和/或空间变化的选择等形式存在的平衡选择，可以解释主要组织相容性复合体（MHC）基因的高度变异性。本文研究了病原体存在与否随时间变化对多等位基因座遗传变异的影响。在基本模型中，对每种病原体的抗性由一个特定等位基因赋予，且该等位基因被假定为显性。假设s是没有抗性等位基因的纯合子（和杂合子）的选择劣势，病原体出现的世代比例为e，那么纯合子的适合度变为(1 - s)((n - 1)e)，杂合子的适合度变为(1 - s)((n - 2)e)，其中n是等位基因的数量。在这种情况下，即使不存在内在的杂合子优势，也满足稳定的多等位基因多态性的条件。等位基因频率的分布以及由此产生的杂合性是病原体在后代中出现的自相关函数。当世代间存在正自相关时，观察到的杂合性会降低。此外，还研究了较低水平的选择和显性效应以及遗传漂变的影响。将这些效应与几个南美印第安样本中两个MHC基因观察到的杂合性进行了比较。总体而言，特定等位基因赋予对随时间变化的病原体的抗性，可能有助于解释在MHC基因和其他类似的宿主防御基因座上观察到的多态性。
