Measuring immunogenetic diversity during the Pleistocene

绝大多数遗传多样性研究都集中在现有种群上。然而，结合古代DNA的种群遗传学研究表明，对于许多物种来说，目前的多样性和多样性分布甚至不能反映最近的过去。到目前为止，几乎所有使用古代DNA的种群遗传分析都依赖于线粒体DNA分析，并测量多样性及其随时间的分布。我们建议调查从晚更新世到全新世(大约6万年的时间跨度)的两个物种的核DNA多样性，以了解免疫上重要的核DNA基因座的核DNA多样性。所选物种之间的主要对比是，其中一种猛犸象(猛犸象)已经灭绝，而麝香在大约10,000年前的更新世末期灭绝后幸存下来，当时欧亚和美洲的大多数大型动物物种(&gt；30公斤)都消失了。感兴趣的基因座位于主要组织相容性复合体(MHC)和Toll样受体基因(TLRs)，分别代表获得性免疫系统和先天性免疫系统。这些基因的多样性对于宿主抵御病原体至关重要。MHC多样性的变化与寄生虫载量和对病毒感染的抵抗力等因素有关。TLR多样性的进化通常在非灵长类动物中表现得不那么好，但与MHC多样性一样，与对传染病的抵抗力的变化有关。先天免疫基因和获得性免疫基因的多样性降低与对病原体的易感性有关，如果采取极端措施，可能会导致物种下降。在对数百个样本进行分析后，猛犸象和麝香是线粒体DNA多样性方面最具特征的两个物种。我们建议对以前以线粒体多样性为特征的猛犸象和麝香的MHC和TLR多样性进行表征，以检查空间和时间上的变化。获得的数据集将代表在已知线粒体多样性的背景下对免疫遗传多样性进行的第一次长期进化分析，这些线粒体多样性是现有的两个最大的古代DNA集合。我们希望确定两个物种的TLR和MHC等位基因的进化率、持久性和替换率，这将提供更好的了解从现代DNA检查中无法获得的基因座的进化动力学。鉴于麝牛和猛犸象在特定时间点具有相同的人口统计模式，而在其他时间点又存在差异，这种比较将为阐明免疫遗传进化的一般原理提供背景，例如证明类似的人口统计变化是否会导致类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.