title: Ser/Thr-rich domains are associated with genetic variation and morphogenesis in Saccharomyces cerevisiae.
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.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bowen
authors.forename: Alan E
authors.initials: AE
authors.lastname: Wheals
mesh_terms: D016000:Cluster Analysis; D014644:Genetic Variation; D016681:Genome, Fungal / Q000235:genetics*; D016366:Open Reading Frames; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D020080:Tandem Repeat Sequences; D013912:Threonine / Q000235:genetics*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013912:Threonine; D012694:Serine; D017346:Protein Serine-Threonine Kinases