Transcription factor evolution in eukaryotes and the assembly of the regulatory toolkit in multicellular lineages

Abstract

Transcription factors (TFs) are the main players in transcriptional regulation in eukaryotes. However, it remains unclear what role TFs played in the origin of all of the different eukaryotic multicellular lineages. In this paper, we explore how the origin of TF repertoires shaped eukaryotic evolution and, in particular, their role into the emergence of multicellular lineages. We traced the origin and expansion of all known TFs through the eukaryotic tree of life, using the broadest possible taxon sampling and an updated phylogenetic background. Our results show that the most complex multicellular lineages (i.e., those with embryonic development, Metazoa and Embryophyta) have the most complex TF repertoires, and that these repertoires were assembled in a stepwise manner. We also show that a significant part of the metazoan and embryophyte TF toolkits evolved earlier, in their respective unicellular ancestors. To gain insights into the role of TFs in the development of both embryophytes and metazoans, we analyzed TF expression patterns throughout their ontogeny. The expression patterns observed in both groups recapitulate those of the whole transcriptome, but reveal some important differences. Our comparative genomics and expression data reshape our view on how TFs contributed to eukaryotic evolution and reveal the importance of TFs to the origins of multicellularity and embryonic development.phylotypic stage | Holozoa | LECA T ranscription factors (TFs) are proteins that bind to DNA in a sequence-specific manner (1) and enhance or repress gene expression (2-4). In response to a broad range of stimuli, TFs coordinate many important biological processes, from cell cycle progression and physiological responses, to cell differentiation and development (5, 6). Thus, TFs have a central role in the transcriptional regulation of all cellular organisms, being present in all branches of the tree of life (bacteria, archaea, and eukaryotes). There appears to be a correlation between elaborate regulation of gene expression and the complexity of organisms (7), such that the amount (as a proportion of an organism's total gene content) and diversity of TF proteins is expected to be directly correlated with this complexity (8). Indeed, TFs play a crucial role in multicellular eukaryotes. For example, TFs are the master regulators of embryonic development in embryophytes and metazoans (9), and analyses of their embryonic transcriptional profiles support the presence of a phylotypic stage in both lineages (10-14). These studies have also shown that evolutionarily younger genes tend to be expressed at earlier and later stages of development, whereas the transcriptomes of the middle stages (the phylotypic stage) are dominated by ancient genes (10, 13). It remains to be investigated how the evolutionary age and the expression patterns of the different TFs shift throughout the ontogeny of these lineages and whether TF expression profiles correlate with the general transcriptome profiles.Previous studies have analyzed the evolutionary ...

Cnidarian cell type diversity revealed by whole-organism single-cell RNA-seq analysis

“…Moreover, analysis of evolutionary conservation showed that 85% of the identified TFs are metazoan innovations (Wallberg et al, 2004), with candidates for cnidarian or Nematostella novelties represented in all structural classes, but enriched for C2H2 zinc fingers (p<<0.0001, chi-square). These results emphasize the relevance of metazoan TF innovations in animal cell type function, and in particular of the metazoan-expanded homeobox TF class (de Mendoza et al, 2013).not peer-reviewed) is the author/funder. All rights reserved.…”

“…Additionally, we predicted for each protein the Pfam domain composition using Pfamscan (Punta et al, 2012) with default curated gathering threshold. Nematostella TFs were identified using univocal Pfam domains for each structural TF family (de Mendoza et al, 2013). In the case of multi-TF families (Homeobox, Fox, bHLH, bZIP, DM, Smad, Myb, NR, RFX, RHD, SRF, Ets, T-box and Sox), we used phylogenetic analyses for each family in order to classify them into specific subfamilies (together with the complete TF sets of additional 10 animal species, including Homo sapiens and Drosophila melanogaster for reference annotation).…”

Gene Regulatory Networks for the Haploid-to-Diploid Transition of Chlamydomonas reinhardtii

“…choanoflagellates) and Embryophyta (e.g. charophytes) have indeed reported that many GRN components predate the origins of the crown groups (Fairclough et al, 2013;Hori et al, 2014;King et al, 2008;de Mendoza et al, 2013;Wickett et al, 2014;Worden et al, 2009). These findings encourage inquiry into the roles of pan-eukaryotic GRN modules in the differentiation repertoires of the unicellular eukaryotes that share common ancestry with crown group organisms.…”

Exploring the bZIP regulatory network in the sponge Amphimedon queenslandica: insights into the ancestral animal regulatory genome

“…in Degnan et al, 2009;Larroux et al, 2008b;Richards, 2010), many others have an older origin and are found in unicellular and colonial holozoans, or in all eukaryotes (e.g. in Best et al, 2004;de Mendoza et al, 2013;GamboaMelendez et al, 2013;King, 2004;Sebe-Pedros et al, 2011). The sequencing of the Capsaspora owczarzaki genome (Suga et al, 2013) revealed an extensive repertoire of TF domains in this filasterian, including bHLH, bZIP, HMG box, MADS-box, Homeobox, Forkhead, CP2, p53, STAT DNA binding and Churchill, T-box, Runt, and the Rel homology domains (Sebe-Pedros et al, 2011).…”