Trinucleotide repeats are clustered in regulatory genes in Saccharomyces cerevisiae

The genome of Saccharomyces cerevisiae contains numerous unstable microsate llite sequences. Mononucleotide and dinucleotide repeats are rarely found i n ORFs, and when present in an ORF are frequently located in an intron or a t the C terminus of the protein, suggesting that their instability is delet erious to gene function. DNA trinucleotide repeats (TNRs) are found at a hi gher-than-expected frequency within ORFs, and the amino acids encoded by th e TNRs represent a biased set. TNRs are rarely conserved between genes with related sequences, suggesting high instability or a recent origin. The gen es in which TNRs are most frequently found are related to cellular regulati on. The protein structural database is notably lacking in proteins containi ng amino acid tracts, suggesting that they are not located in structured re gions of a protein but are rather located between domains. This conclusion is consistent with the location of amino acid tr-acts in two protein famili es. The preferred location of TNRs within the ORFs of genes related to cell ular regulation together with their instability suggest that TNRs could hav e an important role in speciation. Specifically, TNRs could serve as hot sp ots for recombination leading to domain swapping, or mutation of TNRs could allow rapid evolution of new domains of protein structure.