Dimerizing Eukaryotic Transcription Factor Family Evolution and Biological Complexity
Final Report Abstract
Evolution of biological complexity, such as multicellularity, is intimately related to adaptation at the level of gene regulation which in turn employs transcription factors (TFs). More complex organisms such as higher metazoa have more TFs than simpler ones. Eukaryotes further enrich their regulatory repertoire by TF modularity through alternative splicing, protein domain rearrangements, and, above all, alternating dimerization in the formation of regulatory complexes. Here, we set out to understand how TF family expansions occur and can be utilized in the course of evolution. For this purpose we analyzed the five largest TF families in more than 30 metazoan species. Interestingly, these TF families all represent dimerizing TF families. These families comprised bHLH, bZIP, znF, homeobox and Nuclear Receptors. First, we found that TF families expand continually in nearly all lineages, underlining the high adaptive potential of these families. Whole genome duplications had a particularly profound effect on their expansion which indicates that TF duplicates are more often retained than genes coding for other protein families. Second, rearrangements of domains in bHLH sub-families in particular could be linked to the emergence of novel functions which we estimated by analyzing the associated GO terms. This underscored the high evolutionary potential and adaptive innovation which domain rearrangements can have and shows clearly that protein domains, not genes, are the units of selection. Domain rearrangements 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. Third, we could identify a couple of branches in the metazoan species tree along which, independently from whole-genome duplications, TF families experience exceptional family-specific accelerated expansions. Finally, by analyzing expression data of TF families, we conclude that, following functional shifts triggered by domain rearrangements, cis-regulatory changes accomplish widespread fine-tuning of the function of TFs. Interestingly, the initial functional determination does not play a role and it seem as if almost every new TF can be recruited to and new functional regime. In conclusion, both cis- and trans-changes jointly contribute to the functional diversification of TFs although at different time scales and with different effects on the evolutionary potential of TFs.
Publications
- Evidence of interaction network evolution by wholegenome duplications: A case study in mads-box proteins. Molecular Biology and Evolution, 24(3):670– 678, 2007
A. S. Veron, K. Kaufmann, and E. Bornberg-Bauer
- Evolution of regulatory networks. In: Genetics, Genomics, Proteomics and Bioinformatics. John Wiley & Sons, 2007
A. S. Veron and E. Bornberg-Bauer
- One billion years of bzip transcription factor evolution: Conservation and change in dimerization and DNA-binding site specificity. Molecular Biology and Evolution, 24(3):827–835, Mar. 2007
G. Amoutzias, A. Veron, J. Weiner, M. Robinson-Rechavi, E. Bornberg-Bauer, S. Oliver, and D. Robertson
- Studying the evolution of regulatory networks. In: F. Kepes, editor, Biological Networks. World Scientific, 2007
A. Veron, D. Whitehead, and E. Bornberg-Bauer
