Potts W K, Manning C J, Wakeland E K
Center for Mammalian Genetics, University of Florida, Gainesville 32610.
Philos Trans R Soc Lond B Biol Sci. 1994 Nov 29;346(1317):369-78. doi: 10.1098/rstb.1994.0154.
In house mice, and probably most mammals, major histocompatibility complex (MHC) gene products influence both immune recognition and individual odours in an allele-specific fashion. Although it is generally assumed that some form of pathogen-driven balancing selection is responsible for the unprecedented genetic diversity of MHC genes, the MHC-based mating preferences observed in house mice are sufficient to account for the genetic diversity of MHC genes found in this and other vertebrates. These MHC disassortative mating preferences are completely consistent with the conventional view that pathogen-driven MHC heterozygote advantage operates on MHC genes. This is because such matings preferentially produce MHC-heterozygours progeny, which could enjoy enhanced disease resistance. However, such matings could also function to avoid genome-wide inbreeding. To discriminate between these two hypotheses we measured the fitness consequences of both experimentally manipulated levels of inbreeding and MHC homozygosity and heterozygosity in semi-natural populations of wild-derived house mice. We were able to measure a fitness decline associated with inbreeding, but were unable to detect fitness declines associated with MHC homozygosity. These data suggest that inbreeding avoidance may be the most important function of MHC-based mating preferences and therefore the fundamental selective force diversifying MHC genes in species with such mating patterns. Although controversial, this conclusion is consistent with the majority of the data from the inbreeding and immunological literature.
在家鼠以及可能大多数哺乳动物中，主要组织相容性复合体（MHC）基因产物以等位基因特异性方式影响免疫识别和个体气味。虽然一般认为某种形式的病原体驱动的平衡选择是MHC基因前所未有的遗传多样性的原因，但在家鼠中观察到的基于MHC的交配偏好足以解释在该物种和其他脊椎动物中发现的MHC基因的遗传多样性。这些MHC异配交配偏好与病原体驱动的MHC杂合优势作用于MHC基因的传统观点完全一致。这是因为这种交配优先产生MHC杂合后代，这些后代可能具有更强的抗病能力。然而，这种交配也可能起到避免全基因组近亲繁殖的作用。为了区分这两种假设，我们在野生家鼠的半自然种群中测量了实验控制的近亲繁殖水平以及MHC纯合性和杂合性对适应性的影响。我们能够测量到与近亲繁殖相关的适应性下降，但无法检测到与MHC纯合性相关的适应性下降。这些数据表明，避免近亲繁殖可能是基于MHC的交配偏好的最重要功能，因此是使具有这种交配模式的物种中MHC基因多样化的基本选择力量。尽管存在争议，但这一结论与来自近亲繁殖和免疫学文献的大多数数据一致。
