SELECTIVE MECHANISMS MAINTAINING H-2 POLYMORPHISMS

主要组织相容性的1类和11类基因产物 复合体(MHC)将外来抗原递送给T淋巴细胞，并 因此，这是免疫反应的重要组成部分。这些基因是 也是脊椎动物已知的最多态的基因座。它有 一般认为，这种维护是史无前例的 遗传多样性是由于 不同种类的病原体和寄生虫，它们各自都是地方病 物种。然而，其中一个最关键的失败 预测，对特定传染病的易感性 应该与某些MHC等位基因相关，造成了混乱。 各种各样的数据表明，这些多态是 通过某种形式的强平衡维持在自然种群中 选择。尽管已经假设了许多选择性机制 为了维护这些多态，几乎没有 在确定哪些机制方面取得了进展 实际上对自然种群中的MHC基因起作用。我们建议 直接衡量维持MHC的选择性机制 通过分析圈养野鼠的健康成分来实现多样性 人口。这种总体级别的方法允许测试 永远无法在实验室中检验的假设(例如 与频率相关的假设)，并将直接回答 MHC基因多态如何影响适合度的基本问题 关于个人的。我们将检查以下健身要素。 MHC基因分型对不同病死率的影响 繁殖成功将被衡量。这些数据将允许 检验许多基于疾病的假设，如杂合子 优势和频率相关的选择。交配偏好 将通过观察和观察确定附件内的 亲子关系排除技术(例如，遗传指纹)。 交配偏好也将在实验室进行测试，这是 将允许控制自然环境中固有的混杂变量 社会制度。有利于MHC杂合子的传输失真 将通过检查信息丰富的实验室匹配来进行测试 出生时与孟德尔人预期的偏差。人口 遗传学模型表明，MHC多态的维持 需要相对极端的选择级别，运行 在生存或生殖特征上。我们对这个问题的无知 这种选择的方式是我们对如何选择的一个重大差距 病原体和脊椎动物的免疫系统相互作用。

Class 1 and 11 gene products of the major histocompatibility complex (MHC) present foreign antigens to T-lymphocytes and are thus essential components of the immune response. These genes are also the most polymorphic loci known for vertebrates. It has generally been assumed that the maintenance of this unprecedented genetic diversity is due to the selective forces created by the diverse group of pathogens and parasites that are endemic to each species. However, the failure of one of the most critical predictions, that susceptibility to specific infectious diseases should correlate with certain MHC alleles, has created confusion. A wide variety of data indicate that these polymorphisms are maintained in natural populations by some form of strong balancing selection. Although many selective mechanisms have been postulated to contribute to the maintenance of these polymorphisms, little progress has been made towards identifying which mechanisms actually operate on MHC genes in natural populations. We propose to measure directly the selective mechanisms that maintain MHC diversity by analyzing fitness components in a captive wild mouse population. This population level approach allows the testing of hypotheses that could never be tested in the laboratory (e.g. frequency dependent hypotheses) and will directly answer the fundamental question of how MHC polymorphisms affect the fitness of individuals. The following fitness components will be examined. The influence of MHC genotypes on differential mortality and reproductive success will be measured. These data will allow testing of numerous disease based hypotheses such as heterozygote advantage and frequency dependent selection. Mating preferences within the enclosure will be determined through observations and paternity exclusion techniques (e.g. genetic fingerprinting). Mating preferences will also be tested in the laboratory, which will allow control of confounding variables inherent in natural social systems. Transmission distortion favoring MHC heterozygotes will be tested by checking informative laboratory matings for deviations from Mendelian expectations at birth. Population genetics models indicate that the maintenance of MHC polymorphisms requires relatively extreme levels of selection, operating either on survival or reproductive traits. Our ignorance concerning the mode of this selection is a major gap in our understanding of how pathogens and the vertebrate immune system interact.