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Nucleic Acids Res. 2016 Jul 27;44(13):6287-97. doi: 10.1093/nar/gkw492. Epub 2016 Jun 10.

Mechanisms of transcription factor evolution in Metazoa.

Author information

1
Evolutionary Bioinformatics Group, Institute for Evolution and Biodiversity, Hüfferstrasse 1, D-48149 Münster, Germany.
2
Evolutionary Bioinformatics Group, Institute for Evolution and Biodiversity, Hüfferstrasse 1, D-48149 Münster, Germany Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.
3
Evolutionary Bioinformatics Group, Institute for Evolution and Biodiversity, Hüfferstrasse 1, D-48149 Münster, Germany ebb@uni-muenster.de.

Abstract

Transcriptions factors (TFs) are pivotal for the regulation of virtually all cellular processes, including growth and development. Expansions of TF families are causally linked to increases in organismal complexity. Here we study the evolutionary dynamics, genetic causes and functional implications of the five largest metazoan TF families. We find that family expansions dominate across the whole metazoan tree; however, some branches experience exceptional family-specific accelerated expansions. Additionally, we find that such expansions are often predated by modular domain rearrangements, which spur the expansion of a new sub-family by separating it from the rest of the TF family in terms of protein-protein interactions. This separation allows for radical shifts in the functional spectrum of a duplicated TF. We also find functional differentiation inside TF sub-families as changes in expression specificity. Furthermore, accelerated family expansions are facilitated by repeats of sequence motifs such as C2H2 zinc fingers. We quantify whole genome duplications and single gene duplications as sources of TF family expansions, implying that some, but not all, TF duplicates are preferentially retained. We conclude that trans-regulatory changes (domain rearrangements) are instrumental for fundamental functional innovations, that cis-regulatory changes (affecting expression) accomplish wide-spread fine tuning and both jointly contribute to the functional diversification of TFs.

PMID:
27288445
PMCID:
PMC5291267
DOI:
10.1093/nar/gkw492
[Indexed for MEDLINE]
Free PMC Article

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