Doctoral Dissertation Improvement: The Effect of Interspecific Hybridization on MHC Diversity in Wild Baboons

在对抗病原体的“军备竞赛”中，拥有较少常见的免疫基因可能是有利的。传染性病原体可能已经进化到可以逃避更常见变种的防御，使得具有罕见变种的生物体更有可能存活下来。在灵长类动物中，像所有脊椎动物一样，许多对免疫系统至关重要的蛋白质是由主要组织相容性复合体（MHC）编码的，MHC参与抵抗艾滋病毒和结核病等病原体。具有罕见形式的优势使MHC基因复合体成为人类基因组中最多样化的区域之一。最近，研究人员发现，当一些现代人的祖先与一种已灭绝的古人类杂交时，至少有一种MHC变体进入了人类基因库。这种新形式的罕见性可能促进了MHC变体在人群中的引入和传播。为了更好地理解杂交对MHC的影响，在Todd Disotell博士的指导下，博士生Christina Bergey（纽约大学）的这项研究侧重于两种狒狒在埃塞俄比亚成功杂交的自然实验。利用最新的DNA测序技术，MHC基因座被遗传分型，来自杂交区个体的数千个中性标记被用来测试MHC等位基因是否能够在亲本群体中转移和广泛传播。埃塞俄比亚狒狒杂交区提供了一个理想的机会，在适当的灵长类动物模型中探索选择和杂交对MHC多样性的影响。这项研究增加了我们对杂交的理解，这种现象已经多次影响了我们的血统。它还提供了灵长类MHC变异的进化背景，这具有行为，免疫学和生物医学的重要性。DNA序列存储在公开可用的数据库中，所有软件都在网上免费提供，并在开源许可下发布。由于增加公众对进化论的理解是人类学研究的一个基本目标，因此在项目的实施中也采用了宣传结果的新形式。

In the 'arms race' against pathogens, having less common immune genes can be advantageous. Infectious agents may have evolved to evade the defenses of the more common varieties, making organisms with rare variants more likely to survive. In primates, like all vertebrates, many proteins essential to the immune system are encoded by the Major Histocompatibility Complex (MHC), which is involved in resistance to pathogens such as HIV and tuberculosis. The advantage of having rare forms has made the MHC gene complex one of the most diverse regions in the human genome. Recently, researchers found that at least one variant of the MHC entered the human gene pool when the ancestors of some modern humans interbred with an extinct hominin. The novel form's rarity may have facilitated the introduction and spread of the MHC variant through the population. To better understand the effects of hybridization on MHC, this research by doctoral student Christina Bergey (New York University), under the guidance of Dr. Todd Disotell, focuses on a natural experiment in which two species of baboons successfully interbreed in Ethiopia. Using the latest DNA sequencing techniques, MHC loci are genetically typed and thousands of neutral markers from individuals across the hybrid zone are utilized to test whether MHC alleles are able to transfer and spread widely throughout the parental population. The Ethiopian baboon hybrid zone offers an ideal opportunity to explore the influence of selection and hybridization on MHC diversity in an appropriate primate model. The study increases our understanding of hybridization, a phenomenon that has affected our lineage numerous times. It also provides evolutionary context to primate MHC variation, which has behavioral, immunological, and biomedical importance. DNA sequences are deposited in publicly available databases and all software is made freely available online and released under open source licenses. Since increasing public understanding of evolution is an essential goal of anthropological research, new forms of outreach to publicize the results also are employed in the conduct of the project.