The vertebrate immune system includes numerous proteins involved in the recognition and elimination of parasitic organisms. The general goals of this research are to understand the evolution of key molecular components of this system, especially the molecules encoded by the genes of the major histocompatibility complex (MHC), and to understand how immunogenic proteins of parasitic organisms have evolved under natural selection exerted by the host~s immune system. The MHC is a multi-gene family encoding cell-surface glycoproteins which play an important role in the immune system, binding foreign peptides and presenting them to T cells. Certain MHC loci are polymorphic in humans and other vertebrates, and our analyses of DNA sequence data have provided evidence that this polymorphism is maintained by positive selection favoring diversity in the peptide binding region of the MHC molecule and thus, presumably, favoring the ability to bind a variety of foreign peptides. Therefore the MHC provides an excellent system for studying the evolution of immune recognition and the role of infectious disease as an agent of natural selection. The methods involve statistical analysis of published DNA sequences, of which there are a large number for MHC genes of several mammalian species; for other immune system genes; and for the genes of parasites encoding immunogenic proteins. The purposes of these analyses are as follows: (1) to test the hypothesis that MHC polymorphism is maintained by overdominant selection (heterozygote advantage) relating to disease resistance; (2) to understand the relative roles of long-term persistence of polymorphism and of convergent evolution in contributing to MHC polymorphisms shared by different mammalian species; (3) to test the hypothesis that peptides presented by MHC molecules tend to be derived from highly conserved portions of generally conserved proteins); (4) to test the hypothesis that the vertebrate immune system has exerted selection on the proteins of parasitic organisms to evade recognition by the host; (5) to test the hypothesis that, in mammals, proteins expressed in the immune system evolve more rapidly than those expressed in other tissues; and (6) to understand the roles of gene duplication, interlocus recombination, and natural selection in the diversification of immune system gene families (including the MHC, complement components, the proteasome components, the chemokines, the C-type lectins, natural resistance associated macrophage proteins, and the protein tyrosine kinases).
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