functional diversification of paralogous transcription factors via divergence in dna binding site motif and in expression功能多样化paralogous转录因子通过dna结合位点的主题和散度表达式.pdfVIP

Functional Diversification of Paralogous Transcription Factors via Divergence in DNA Binding Site Motif and in Expression Larry N. Singh, Sridhar Hannenhalli* Penn Center for Bioinformatics, Department of Genetics, University of Pennsylvania, Philadephia, Pennsylvania, United States of America Abstract Background: Gene duplication is a major driver of evolutionary innovation as it allows for an organism to elaborate its existing biological functions via specialization or diversification of initially redundant gene paralogs. Gene function can diversify in several ways. Transcription factor gene paralogs in particular, can diversify either by changes in their tissue-specific expression pattern or by changes in the DNA binding site motif recognized by their protein product, which in turn alters their gene targets. The relationship between these two modes of functional diversification of transcription factor paralogs has not been previously investigated, and is essential for understanding adaptive evolution of transcription factor gene families. Findings: Based on a large set of human paralogous transcription factor pairs, we show that when the DNA binding site motifs of transcription factor paralogs are similar, the expressions of the genes that encode the paralogs have diverged, so in general, at most one of the paralogs is highly expressed in a tissue. Moreover, paralogs with diverged DNA binding site motifs tend to be diverged in their function. Conversely, two paralogs that are highly expressed in a tissue tend to have dissimilar DNA binding site motifs. We have also found that in general, within a paralogous family, tissue-specific decrease in gene expression is more frequent than what is expected by chance. Conclusions: While previous investigations of paralogous gene diversification have only considered coding sequence divergence, by explicit