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

博士论文改进：种间杂交对野生狒狒MHC多样性的影响

• 批准号: 1260816
• 负责人: Todd Disotell
• 金额: $ 3.12万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1260816&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Effect; Interspecific

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.

在对抗病原体的“军备竞赛”中，拥有较少的常见免疫基因可能是有利的。感染性病原体可能已经进化到逃避更常见的品种的防御，使具有罕见变异的生物体更有可能生存。在灵长类动物中，像所有脊椎动物一样，免疫系统所必需的许多蛋白质由主要组织相容性复合物（MHC）编码，该复合物参与抵抗病原体，如HIV和结核病。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。 为了更好地了解杂交对MHC的影响，博士生Christina Bergey（纽约大学）在托德·迪索特尔博士的指导下进行了这项研究，重点是埃塞俄比亚两种狒狒成功杂交的自然实验。使用最新的DNA测序技术，MHC基因座的基因分型和成千上万的中性标记，从整个杂交区的个人被用来测试是否MHC等位基因能够转移和广泛传播整个父母的人口。埃塞俄比亚狒狒杂交区提供了一个理想的机会，探讨选择和杂交的影响，在适当的灵长类动物模型的MHC多样性。 这项研究增加了我们对杂交的理解，这种现象多次影响了我们的血统。它还提供了进化背景灵长类动物的MHC变异，这具有行为，免疫学和生物医学的重要性。DNA序列存放在公开的数据库中，所有软件都在网上免费提供，并在开源许可证下发布。由于增加公众对进化的了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新的外联形式来宣传成果。