Title: The evolution of classical type MHC class I genes in the gray short-tailed opossum, Monodelphis domestica.
Authors: Tracey Williams1, Alana Sharp2, and Robert Miller2
Affiliations: 1Department of Chemistry, Fort Lewis College, 2Center for Evolutionary and Theoretical Immunology, University of New Mexico
Abstract: The major histocompatibility complex (MHC) is a cluster of genes that is the most polymorphic and gene-dense region in vertebrate genome. The MHC was discovered because of its vital role to vertebrate immunity. There are three classes of loci that make up the MHC which are Class I, II, and III. This project investigates the evolution of genes in the Class I category. Class I genes can be further subdivided into classical and non-classical. Classical class I molecules are ubiquitously expressed, highly polymorphic, and their role is to present intracellularly-derived antigens to CD8+ T-cells. Non-classical MHC genes are significantly less polymorphic and are involved in a variety of immune and non-immune roles. To investigate the evolution of classical Class I genes further, comparative genomics has been performed. Marsupials are humans most distant relatives within the Therian lineage of mammals, sharing a last common ancestor nearly 145 million years ago. The MHC region has been investigated in detail for only one marsupial, Monodelphis domestica, a species for which there is a complete genome sequence. In initial analysis of the opossum MHC, there appeared to be only a single classical class I, called Modo-UA1. However analysis of UA1 diversity revealed more alleles per individual than could be accounted for by a single locus. Two additional loci, called UA3 and UA4, were revealed in a newer genome assembly. To confirm the existence of these two additional loci, PCR amplification of the UA genes present in individual opossums was performed, followed by DNA sequencing and analysis to determine how many alleles are present in single animals. Genomic DNA from both captive and wild populations was used.