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Research focus in the Thomas lab has recently shifted to molecular evolution, especially the evolution and function of gene families implicated in environmental interactions and other rapidly changing selective pressures. Work is mostly on nematode and mammalian gene families, with some comparative analyses to other groups.
Gene families are abundant and pervasive in multicellular organisms, where they arise by duplication and diversification of existing genes. The mechanism of duplication and the patterns of diversification that occur subsequent to duplications are poorly understood and probably underlie critical aspects of organismal evolution. Our analysis of positive selection (natural selection to change amino acid sequence) indicates that genes in many families undergo rapid change at specific protein sites. The patterns of these changes often provide strong insight into the function and evolution of the genes. For example, in nematodes and plants, most of the large families of substrate specificity adapter proteins for poly-ubiquitination are under strong positive selection in their substrate-binding domain. This pattern suggests that the adapter substrates have changed over time and that the adapter proteins are selected to maintain substrate binding. A simple explanation is that these proteins function in innate immunity to target foreign proteins for proteolysis. Another example is the rapidly expanded C2H2 (Kruppel-like) zinc finger protein family in mammals, many members of which are under subject to strong positive selection in the nucleotide contacting residues of the zinc fingers. The patterns of family expansion and positive selection suggest that many mammalian zinc finger genes have been selected to increase family complexity (gene number) and to change their regulatory targets (DNA binding specificity). These changes may contribute to the evolutionary plasticity of morphology and development in mammals.
Copyright © 2003-2013 Molecular & Cellular Biology Program, University of Washington
Fred Hutchison Cancer Research Center | University of Washington
Institute for Systems Biology | Seattle Biomed