Pervasive Variation of Transcription Factor Orthologs Contributes to Regulatory Network Evolution

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The phenotypic differences observed between closely related organisms are thought to be due largely to changes in regulatory networks. Changes in transcriptional networks can occur via mutations in cis binding sites, for which there are numerous known examples, as well as via binding specificity variation in transcription factors (TFs), a less studied phenomenon that has been observed primarily in multi-gene families. Though large-scale experimental studies ascertaining the extent to which TFs contribute to regulatory network variation across organisms are lacking and would be time-consuming, computational methods can begin to address this challenge. Here, we present a systematic, large-scale analysis of DNA-binding specificity evolution in TF orthologs by computationally leveraging specific features of Cys2-His2 zinc finger proteins, the largest class of TFs in animals and major components of their regulatory programs. We find not only that divergence of DNA-binding residues in 1-to-1 orthologous C2H2-ZFs is pervasive but also that these changes show evidence of functional constraint and occur in a gradual, evolutionarily viable manner. We conclude that the diversification of orthologous TFs has most likely played a major and largely unstudied role in gene regulatory network evolution in metazoans.

Vyšlo v časopise: Pervasive Variation of Transcription Factor Orthologs Contributes to Regulatory Network Evolution. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005011
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005011

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