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General Departmental Seminar Series

Evolutionary Dynamics of Human Genes: Implications for Understanding Cancer-Related Genes

Michael A. Thomas, Ph.D., Bioinformatics Research Center, Medical College of Wisconsin

Friday, April 11, 2003, 12 p.m.

6225 Medical Sciences Center (CSSC), 1300 University Avenue


We measured the relative intensity of purifying selection experienced by 3131 human genes, representing about 10% of the human genome. The genes were distributed evenly across the genome in a pattern similar to a complete collection of Human full-length cDNAs. Selective pressures were inferred from analyses of rates of synonymous and nonsynonymous substitutions relative to rodent orthologues. Overall, human genes experienced extremely strong purifying selection, with the nonsynonymous substitution rate about 1/10th the synonymous substitution rate with a large amount of variation. Groups of genes were defined using standard cellular component and molecular function classifications identified by the Gene Ontology Consortium. A number of these groups differed significantly from the overall mean for human genes, including five molecular functions (immune system, transciption, enzyme, nucleic acid binding, and transporter genes), and two cellular components (extracellular and intracellular proteins). Human cancer-related genes (oncogenes & tumor suppressor genes) experienced stronger intensities of purifying selections than most "normal" human genes and other groups of disease-related genes. This result is partially explained by an understanding of human "essential" genes - homologues of mouse genes determined to be lethal in knock-out experiments.

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