Gene duplication and co-evolution of G1/S transcription factor specificity in fungi are essential for optimizing cell fitness

PLoS Genet. 2017 May 15;13(5):e1006778. doi: 10.1371/journal.pgen.1006778. eCollection 2017 May.

Abstract

Transcriptional regulatory networks play a central role in optimizing cell survival. How DNA binding domains and cis-regulatory DNA binding sequences have co-evolved to allow the expansion of transcriptional networks and how this contributes to cellular fitness remains unclear. Here we experimentally explore how the complex G1/S transcriptional network evolved in the budding yeast Saccharomyces cerevisiae by examining different chimeric transcription factor (TF) complexes. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. The difference in size and complexity of the G1/S transcriptional network across yeast species makes it well suited to investigate how TF paralogs (SBF and MBF) and DNA binding sequences (SCB and MCB) co-evolved after gene duplication to rewire and expand the network of G1/S target genes. Our data suggests that whilst SBF is the likely ancestral regulatory complex, the ancestral DNA binding element is more MCB-like. G1/S network expansion took place by both cis- and trans- co-evolutionary changes in closely related but distinct regulatory sequences. Replacement of the endogenous SBF DNA-binding domain (DBD) with that from more distantly related fungi leads to a contraction of the SBF-regulated G1/S network in budding yeast, which also correlates with increased defects in cell growth, cell size, and proliferation.

MeSH terms

  • Binding Sites
  • Evolution, Molecular*
  • G1 Phase / genetics*
  • Gene Duplication*
  • Gene Regulatory Networks
  • Genetic Fitness*
  • Protein Binding
  • S Phase / genetics*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Transcription Factors