Ser/Thr-rich domains are associated with genetic variation and morphogenesis in Saccharomyces cerevisiae

Yeast. 2006 Jun;23(8):633-40. doi: 10.1002/yea.1381.

Abstract

Proteins containing regions of amino acid bias are often found in eukaryotes and are associated with particular functional groups. We have carried out a genomic analysis of yeast proteins containing regions with a significant bias of Ser and Thr residues. Our findings reveal that a high number are cell surface proteins or regulatory proteins involved in many aspects of cell differentiation. Furthermore, in Saccharomyces-related species, a highly significant correlation exists between the frequency of Ser-rich regions and DNA repeats, indicating that their generation may rely on similar factors. Cluster analysis shows that Ser/Thr-rich regions, located within the tandem repeats of cell surface proteins, are encoded to an increased frequency by UCU (Ser) and ACU/ACC (Thr), implying that mutational events that generate iterations could involve these codons. Replication slippage is proposed to be a contributing factor, as mounting evidence suggests that repeat generation in cell surface proteins can occur independently of meiosis. To reinforce this argument, we have discovered a premeiotic association between Mre11p, a nuclease involved in DNA repair, and ORFs encoding Ser/Thr-rich regions. Several macromolecules involved in the glycosylation and phosphorylation of proteins require Ser and Thr residues as binding sites. Ser/Thr-rich regions, through polymorphisms, are associated with the evolution of functional sites, particularly in providing motifs for glycosylation and phosphorylation. These results point to a Ser/Thr-biased somatic mutation mechanism that contributes to rapid evolution in yeast.

MeSH terms

  • Cluster Analysis
  • Genetic Variation
  • Genome, Fungal / genetics*
  • Open Reading Frames
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Serine / genetics*
  • Tandem Repeat Sequences
  • Threonine / genetics*

Substances

  • Saccharomyces cerevisiae Proteins
  • Threonine
  • Serine
  • Protein Serine-Threonine Kinases