Structure and Evolution of the MHC in a Model Marsupial

University Of New Mexico, Albuquerque NM

Investigators

Abstract

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.