Natural selection is one of the evolutionary forces proposed to maintain genetic variation within a population. However, few good examples of selection maintaining variation in a natural population have been found. One convincing example of this type of selection occurs at the major histocompatibility complex (or tissue typing complex). Yet several recently discovered MHC loci, HLA-E and -F, were reported to have significantly less variation than other MHC genes. If so, it is likely that these loci are under the influence of a different type of selection, one that does not maintain variation in a population. Instead, these genes may have undergone a selective sweep or may be evolving neutrally. For this doctoral dissertation research project, the investigator will study the amount of variation in HLA-E and HLA-F using a technique called single-strand conformation polymorphism analysis. Next, she will determine the nucleotide changes responsible for this variation by sequencing variant SSCP bands. Based on patterns of nucleotide diversity and using statistical tests for selection such as the newly developed McDonald-Kreitman test and the HKA test of Richard Hudson. Inferences shall be drawn regarding the selective forces that are influencing these genes.
