9707548 Edwards The Mhc (major histocompatibility complex) is a group of genes -- a multigene family -- that help defend vertebrates, including humans, against parasites and infectious disease. In humans and other mammals, various groups of Mhc genes exist, known as families and subfamilies. The most well known of these are called class I and class II. There are 3-5 class II genes in most mammals; these are very distinct from one another, as indicated by the large number of differences one can find between sequences of their DNA. By contrast, the class II genes of birds appear to be much more similar to one another, i.e., less diverse than those of mammals. This similarity is puzzling because diversity among Mhc genes is a major way in which vertebrates are thought to be able to recognize the diversity of infectious agents in nature. It suggests there may be less diversity among genes in birds than in mammals, despite presumably similar needs for protection against parasites. This research will help characterize the similarities and differences among the class II genes in 5 divergent lineages of birds in order to determine whether they have remained distinct as in mammals (the divergent evolution model), or have become similar (homogenized) to one another (the concerted evolution model). These two models can be distinguished by the pattern of phylogenetic relationships of the different bird genes to one another. Class II genes from several songbird species will be isolated and the sequences of these genes will be aligned and compared phylogenetically. The presence of pseudogenes will suggest yet a third model of multigene family evolution, namely the 'birth and death' model. Determining which of these models describes the evolution of Mhc class II genes in birds will help indicate whether the mammalian Mhc is unique in its pattern of evolution, or whether bird Mhc is also characterized by this pattern. Understanding the pattern of multigene family evolution will help yield insig ht into how the genomes of vertebrates evolve. Because Mhc genes are important for resistance to disease, understanding the mechanisms diversifying bird Mhc genes could also be important for conservation of endangered species and for increasing our ability to manipulate disease susceptibility in humans.
