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Tuesday "Noon" Seminar: March 6, 2007Alex Lancaster on "Detecting selection and functional associations in human MHC protein sequences"
12:30-1:45 p.m. in Biosciences West (map of building location), Room 208 |
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Talk Abstract Major histocompatibility complex (MHC) proteins are immunoglobulin-like cell surface receptors which bind both peptides and T cells and mediate the adaptive immune response, in humans they are are known as the human leukocyte antigen (HLA) system. Here I analyse a large multi-locus genotype data set of HLA class I and II data from the from the 13th International Histocompatibility Workshop (IHWS) to identify amino acids that may be under selection. As part of this work I developed a new bioinformatics tool, PyPop, to analyse large-scale genotype data from multiple populations. This analysis found, in agreement with previous work, that there is strong evidence of balancing selection on amino acid sites using the Ewens-Watterson test; however, many sites are highly correlated. Some individual sites or groups of sites appear to be evolving independently with divergent patterns of selection. Key pairs of sites which are ligands for receptors on NK cells are under strong balancing selection and are in strong association with each other, suggesting that NK cells may have shaped variation in certain parts of the molecule more than conventional peptide and T cell interactions. |
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