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

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.