Project Report

Identifying the rate of mutation and the strength of natural selection of immune genes In birds. Many studies have investigated the rate of mutation and the strength of natural selection of immune genes in primates, particularly mammals. The group of genes most often studied belongs to the Major Histocompatibility Complex (MHC), also known as the Human Leukocyte Antigen (HLA). The MHC is a useful genetic system with which to study evolution because it is the most polymorphic functional genetic region in all vertebrates (most functional genes have relatively little variation because selective pressure has eliminated all but the most "fit" gene sequences). The unusual variation in the MHC is attributed to the "arms race" between pathogens and their hosts. As hosts evolve immune defenses, pathogens evolve ways around them. This is known as balancing, or, diversifying selection. Little is known about the evolution of the MHC in non-mammalian species. The MHC in birds has been shown to be much smaller than that of mammals, and it has been hypothesized that the bird MHC represents the more ancient genomic architecture of this gene cluster. By gaining a better understanding of how the MHC has evolved in birds, we can better explain the evolution of MHC in all vertebrates. Specifically, we are interested in calculating a global estimate for the mutation rate and the strength of selection in one of the oldest orders of birds, the Galliformes. Because the bird MHC has many fewer genes than mammals, we are interested in finding out if it is under stronger selection. We estimated evolutionary parameters by using sequences from four closely related species: the domestic chicken, the domestic turkey, the Japanese quail and the ring-necked pheasant Our preliminary estimates suggest that the MHC of birds has a slightly higher mutation rate than other genes and that the strength of selection on the bird MHC is higher than that of mammals. Our calculated mutation rate suggests that the MHC of birds may represent a "mutational hotspot", that is, a genetic region that displays more mutations than expected by chance. While further work needs to be done to verify our findings, the result is exciting in that there are relatively few examples of hot spots in any vertebrate genome. Furthermore, our results indicate that the MHC in birds has been under more selective pressure than the MHC of mammals. This finding is important because it allows us to investigate how the MHC evolves over millions of years in a gene cluster that is extremely small relative to mammals (about 1/20th the size). Insights into microevolution can be gained by examining the MHC of birds more closely in future studies. The award for this project was for two and one-half months, far to little time to complete a study of this scope. However, by beginning the work, I established a relationship with my current supervisor, Dr. Yoko Satta. Dr. Satta has invited me back to Japan to continue our collaboration. Thus, while we were unable to complete the analysis during the project time period, we are now working full time together on the project and will publish our findings later this year. In addition, work on this project led to new international collaborations. Dr. Andrea Townsend of UC-Davis and Dr. Nishiumi of the National Museum of Japan have joined our research team. Thus, the research begun by this relatively small project has led to a very large project that brings scientists together from across the globe. It is our intention to continue to build our collaborative effort over the next several years.

National Science Foundation (NSF)
Office of International and Integrative Activities (IIA)
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Carter Kimsey
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Eimes, John A
United States
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