Structure and Evolution of the MHC in a Model Marsupial

主要组织相容性复合体（MHC）是一组基因，控制免疫反应的许多方面，包括对传染病的抵抗力和/或易感性。MHC还与许多其他生物现象有关，从怀孕的成功或失败到行为和通过气味识别亲属。这个项目将在一个比以前更大的进化时间尺度上研究哺乳动物MHC基因的进化和功能。该项目将描述一种有袋动物——短尾负鼠模型物种的MHC的含量和多样性。有袋动物，如负鼠和袋鼠，属于大约1.2亿年前从胎盘哺乳动物（如人类和老鼠）中分离出来的一个谱系。负鼠基因组中含有MHC的区域将被克隆，其基因含量将被确定，并最终测序。负鼠MHC中存在的基因将被分析在不同发育阶段的不同组织中的表达，以深入了解它们的功能作用。MHC是人类基因组中基因最丰富的区域。要了解它的进化，就需要对近亲物种进行比较。该项目产生的有袋动物MHC数据将首次为哺乳动物不同亚类之间的比较提供机会。在更广泛的背景下，有袋动物免疫系统的研究也提供了传统哺乳动物模型无法获得的独特机会。有袋动物与胎盘哺乳动物的主要区别在于繁殖和发育；它们生下的幼崽不太成熟，必须在育儿袋中完成发育。这给有袋动物带来了免疫问题，比如如何保护新生儿，一旦它在育儿袋里。要了解这些问题是如何在不同物种中解决的，需要对它们的免疫系统有更多的了解。这项研究项目将是对有袋动物免疫系统的主要组成部分之一MHC的首次大规模研究。该项目也是一项正在进行的研究计划的一部分，该计划涉及与澳大利亚研究人员的国际合作。这个研究项目涉及大量的学生，包括研究生和本科生，在过去的这些国际合作中，并将继续这样做。

The Major Histocompatibility Complex (MHC) is a set of genes that controls many aspects of immune responses including resistance and/or susceptibility to infectious diseases. The MHC has also been linked to many other biological phenomena ranging from the success or failure of pregnancy to behavior and kin recognition by smell. This project will be to study the evolution and function of the MHC genes in mammals over a larger evolutionary time-scale than has been done previously. The project will characterize the content and diversity of the MHC in a model species of marsupial, the short-tailed opossum. Marsupials, such as opossums and kangaroos, belong to a lineage that separated from placental mammals, such as humans and mice, approximately 120 million years ago. The region of the opossum genome containing the MHC will be cloned, its gene content determined, and ultimately sequenced. The genes present in the opossum MHC will be analyzed for their expression in different tissues at different stages of development to gain insight into their functional roles as well.The MHC is the most gene rich region of the human genome. Understanding its evolution requires comparisons among distantly related species. The data on marsupial MHC generated by this project will provide the first opportunity for comparison between different subclasses of mammals. In a broader context, study of marsupial immune systems also provides unique opportunities not available using traditional mammalian models. Marsupials differ from placental mammals primarily in reproduction and development; they give birth to young that are less mature and must complete development in a pouch. This creates immunological problems for the marsupial, such as how to protect the newborn once it is in the pouch. Understanding how such problems are solved in different species requires greater knowledge of their immune systems. This research project will be the first large-scale investigation of one of the major components of the immune system in a marsupial, the MHC. This project is also part of an ongoing research program involving international collaborations with investigators in Australia. This research program has involved a large number of students, both graduate and undergraduate, in these international collaborations in the past and will continue to do so.