Differential selection after duplication in mammalian developmental genes

Gene duplication provides the opportunity for subsequent refinement of dist inct functions of the duplicated copies. Either through changes in coding s equence or changes in regulatory regions, duplicate copies appear to obtain new or tissue-specific functions. If this divergence were driven by natura l selection, we would expect duplicated copies to have differentiated patte rns of substitutions. We tested this hypothesis using genes that duplicated before the human/mouse split and whose orthologous relations were clear. T he null hypothesis is that the number of amino acid changes between humans and mice was distributed similarly across different paralogs. We used a met hod modified from Tang and Lewontin to detect heterogeneity in the amino ac id substitution pattern between those different paralogs. Our results show that many of the paralogous gene pairs appear to be under differential sele ction in the human/mouse comparison. The properties that led to diversifica tion appear to have arisen before the split of the human and mouse lineages . Further study of the diverged genes revealed insights regarding the patte rns of amino acid substitution that resulted in differences in function and /or expression of these genes. This approach has utility in the study of ne wly identified members of gene families in genomewide data mining and for c ontrasting the merits of alternative hypotheses for the evolutionary diverg ence of function of duplicated genes.