Measuring immunogenetic diversity during the Pleistocene

绝大多数遗传多样性研究都集中在现有的种群上。然而，结合古代DNA的种群遗传学研究表明，许多物种目前的多样性和多样性分布甚至不能反映最近的过去。 迄今为止，几乎所有使用古代DNA的群体遗传分析都依赖于线粒体DNA分析和测量多样性及其随时间的分布。我们建议调查核DNA多样性的两个物种从晚更新世到全新世（约60,000年的时间跨度）的核DNA多样性的免疫重要的核DNA位点。所选物种之间的主要对比是，其中一种是长毛猛犸（Mammuthus mammgenius）已经灭绝，而麝牛（Ovibos moschatus）在大约10，000年前的更新世末期灭绝中幸存下来，当时大多数欧亚和美洲巨型动物（> 30公斤）物种消失。感兴趣的基因座位于分别代表适应性和先天性免疫系统的主要组织相容性复合体（MHC）和Toll样受体基因（TLR）中。这些基因的多样性对宿主防御病原体至关重要。MHC多样性的变化与寄生虫负荷和对病毒感染的抵抗力等因素相关。TLR多样性进化在非灵长类动物中通常不太好表征，但与MHC多样性一样，与对感染性疾病的抗性的变化相关。先天性和适应性免疫基因多样性的减少与对病原体的易感性有关，如果极端的话，可能会导致物种的减少。长毛猛犸和麝牛是线粒体DNA多样性最具特征的两个物种，分析了数百个样本。我们建议在猛犸象和麝牛的MHC和TLR多样性的特点，以前的线粒体多样性，检查随时间和空间的变化。所获得的数据集将代表已知的线粒体多样性的背景下，两个最大的古代DNA的集合可用的免疫遗传多样性的第一个长期的进化分析。我们希望确定这两个物种的TLR和MHC等位基因的进化，持久性和替换的速度，这将提供一个更好的理解，不能从现代DNA的检查获得的基因座的进化动力学。考虑到麝牛和猛犸象在给定的时间点都有相同的人口统计学模式，而在其他时间点则有不同的人口统计学模式，这种比较将为阐明免疫遗传进化的一般原理提供背景，例如证明相似的人口统计学变化是否会引发相似的进化免疫遗传趋势。

The vast majority of genetic diversity studies focus on currently existing populations. However, population genetic studies incorporating ancient DNA have demonstrated for many species that current diversity and diversity distribution does not reflect even the recent past. To date, almost all population genetic analysis using ancient DNA has relied on mitochondrial DNA analysis and on measuring diversity and its distribution over time. We propose to investigate nuclear DNA diversity in two species from the late Pleistocene through the Holocene (an approximate 60,000 year time span) for the nuclear DNA diversity of immunologically important nuclear DNA loci. The major contrast between the chosen species is that one, the woolly mammoth (Mammuthus primigenius) is extinct and the muskoxen (Ovibos moschatus) survived the end Pleistocene extinctions approximately 10,000 years ago which saw the disappearance of most of the Eurasian and American megafaunal (> 30 kg) species. The loci of interest are in the major histocompatibility complex (MHC) and Toll-Like-Receptor genes (TLRs) representing the adaptive and innate immune systems respectively. Diversity in these genes is crucial to host defence against pathogens. Variation in MHC diversity correlates with factors such as parasite load and resistance to viral infection. TLR diversity evolution is generally less well characterized in non-primates but like MHC diversity, is associated with variation in resistance to infectious disease. Reduced diversity in both the innate and adaptive immune genes is associated with susceptibility to pathogens which if taken to extremes could hypothetically result in species declines. The woolly mammoth and the muskox are two of the best characterized species for mitochondrial DNA diversity with hundreds of samples analyzed. We propose to characterize MHC and TLR diversity in mammoths and muskoxen previously characterized for mitochondrial diversity to examine changes over space and time. The data set obtained will represent the first long term evolutionary analysis of immunogenetic diversity in the context of known mitochondrial diversity for two of the largest collections of ancient DNA available. We expect to determine the rate of evolution, persistence and replacement of TLR and MHC alleles for both species which will provide a better understanding of the evolutionary dynamics of the loci that cannot be obtained from examination of modern DNA. Given that muskoxen and mammoths both share demographic patterns at given time points and diverge at others, the comparison will provide context for elucidating general principles of immunogenetic evolution e.g. demonstrate whether similar demographic changes elicit similar evolutionary immnogenetic trends.