The emergence of new genes throughout evolution requires rewiring and extension of regulatory networks. However, the molecular details of how the transcriptional regulation of new gene copies evolves remain largely unexplored. Here we show how duplication of a transcription factor gene allowed the emergence of two independent regulatory circuits. Interestingly, the ancestral transcription factor was promiscuous and could bind different motifs in its target promoters. After duplication, one paralogue evolved increased binding specificity so that it only binds one type of motif, whereas the other copy evolved a decreased activity so that it only activates promoters that contain multiple binding sites. Interestingly, only a few mutations in both the DNA-binding domains and in the promoter binding sites were required to gradually disentangle the two networks. These results reveal how duplication of a promiscuous transcription factor followed by concerted cis and trans mutations allows expansion of a regulatory network.
K.P. acknowledges financial support from TRIPLE I and a Belspo mobility grant from the Belgian Federal Science Policy Office co-funded by the Marie Curie Actions from the European Commission. Research in the lab of K.J.V. is supported by ERC Starting Grant 241426, HFSP programme grant RGP0050/2013, VIB, EMBO YIP programme, KU Leuven Programme Financing, FWO, and IWT. A.V. acknowledges RIKEN for the FPR grant. The work of F.A.K. was supported by a grant of the HHMI International Early Career Scientist Programme (grant #55007424), the Spanish Ministry of Economy and Competitiveness (grant #BFU2012-31329) as part of the EMBO YIP programme, two grants from the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017 (grant #Sev-2012-0208)’ and (grant #BES-2013-064004) funded by the European Regional Development Fund (ERDF), the European Union and the European Research Council (grant #335980_EinME). K.V. is supported by an FWO postdoctoral fellowship. Funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Pougach K, Voet A, Kondrashov F, et al. Duplication of a promiscuous transcription factor drives the emergence of a new regulatory network. Nature Communications. 2014;5. doi:10.1038/ncomms5868
Pougach, K., Voet, A., Kondrashov, F., Voordeckers, K., Christiaens, J., Baying, B., … Verstrepen, K. (2014). Duplication of a promiscuous transcription factor drives the emergence of a new regulatory network. Nature Communications, 5. https://doi.org/10.1038/ncomms5868
Pougach, Ksenia, Arnout Voet, Fyodor Kondrashov, Karin Voordeckers, Joaquin Christiaens, Bianka Baying, Vladimı́R Bénès, et al. “Duplication of a Promiscuous Transcription Factor Drives the Emergence of a New Regulatory Network.” Nature Communications 5 (2014). https://doi.org/10.1038/ncomms5868.
K. Pougach et al., “Duplication of a promiscuous transcription factor drives the emergence of a new regulatory network,” Nature Communications, vol. 5, 2014.
Pougach K, Voet A, Kondrashov F, Voordeckers K, Christiaens J, Baying B, Bénès V, Sakai R, Aerts J, Zhu B, Van Dijck P, Verstrepen K. 2014. Duplication of a promiscuous transcription factor drives the emergence of a new regulatory network. Nature Communications. 5.
Pougach, Ksenia, et al. “Duplication of a Promiscuous Transcription Factor Drives the Emergence of a New Regulatory Network.” Nature Communications, vol. 5, Nature Publishing Group, 2014, doi:10.1038/ncomms5868.