Early Evolution of the T-box Transcription Factor Family

Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16050-5. doi: 10.1073/pnas.1309748110. Epub 2013 Sep 16.


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.

Keywords: Holozoa; Porifera; origin multicellularity; premetazoan evolution; subfunctionalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evolution, Molecular*
  • Fetal Proteins / genetics*
  • Histocytochemistry
  • Mesomycetozoea / genetics*
  • Microarray Analysis
  • Multigene Family / genetics*
  • Phenotype*
  • Phylogeny*
  • Protein Binding
  • Real-Time Polymerase Chain Reaction
  • Species Specificity
  • T-Box Domain Proteins / genetics*
  • Xenopus / genetics*


  • Fetal Proteins
  • T-Box Domain Proteins
  • Brachyury protein