Early evolution of the T-box transcription factor family

Developmental transcription factors are key players in animal multicellularity, being members of the T-box family that are among the most important. Until recently, T-box transcription factors were thought to be exclusively present in metazoans. Here, we report the presence of T-box genes in several nonmetazoan lineages, including ichthyosporeans, filastereans, and fungi. Our data confirm that Brachyury is the most ancient member of the T-box family and establish that the T-box family diversified at the onset of Metazoa. Moreover, we demonstrate functional conservation of a homolog of Brachyury of the protist Capsaspora owczarzaki in Xenopus laevis. By comparing the molecular phenotype of C. owczarzaki Brachyury with that of homologs of early branching metazoans, we define a clear difference between unicellular holozoan and metazoan Brachyury homologs, suggesting that the specificity of Brachyury emerged at the origin of Metazoa. Experimental determination of the binding preferences of the C. owczarzaki Brachyury results in a similar motif to that of metazoan Brachyury and other T-box classes. This finding suggests that functional specificity between different T-box classes is likely achieved by interaction with alternative cofactors, as opposed to differences in binding specificity.This work was supported by an Institució Catalana de Recerca i Estudis Avançats contract, European Research Council Starting Grant ERC-2007-StG-206883, and Grant BFU2011-23434 from the Ministerio de Economía y Competitividad (MINECO) (to I.R.-T.). A.S.-P. was supported by a pregraduate Formación Profesorado Universitario grant from MINECO and a grant from MINECO to perform a research stay at the J.L.G.-S. laboratory. J.L.G.-S. thanks the Spanish and Andalusian Governments for Grants BFU2010-14839, CSD2007-00008, and Proyecto de Excelencia CVI-3488 that funded this study. This work was also supported by a Canadian Institutes of Health Research (CIHR) grant [MOP-111007 (to T.R.H.)]. M. Adamski, M. Adamska, and S.L. acknowledge funding from the core budget of the Sars International Centre for Marine Molecular Biology. M.T.W. was supported by fellowships from CIHR and the Canadian Institute for Advanced Research Junior Fellows Genetic Networks Program.Peer reviewe