Evolution of budding yeast prion-determinant sequences across diverse fungi.
Prions are transmissible self-replicating alternative states of proteins. Four prions ([PSI+], [URE3], [RNQ+] and [NU+]) can be inherited cytoplasmically in Saccharomyces cerevisiae laboratory strains. In the case of [PSI+], there is increasing evidence that prion formation may engender mechanisms to uncover hidden genetic variation. Here, we have analysed the evolution of the prion-determinant (PD) domains across 21 fungi, focusing on compositional biases, repeats and substitution rates. We find evidence for constraint on all four PD domains, but each domain has its own evolutionary dynamics. For [PSI+], the Q/N bias is maintained in fungal clades that diverged one billion years ago, with purifying selection observed within the Saccharomyces species. The degree of Q/N bias is correlated with the degree of local homology to prion-associated repeats, which occur rarely in other proteins (<1% of sequences for the proteomes studied). The evolutionary conservation of Q/N bias in Sup35p is unusual, with only eight other S. cerevisiae proteins showing similar, phylogenetically deep patterns of bias conservation. The [URE3] PD domain is unique to Hemiascomycota; part of the PD domain shows purifying selection, whereas another part engenders bias changes between clades. Also, like for Sup35p, the [RNQ+] and [NU+] PD domains show purifying selection in Saccharomyces species. Additionally, in each proteome, we observe on average several hundred yeast-prion-like domains, with fewest in fission yeast. Our findings on yeast prion evolution provide further support for the functional significance of these molecules.
Harrison
Luke B
LB
Department of Biology, McGill University, Stewart Biology Building, 1205 Docteur Penfield Ave, Montreal, QC, Canada H3A 1B1.
Yu
Zhan
Z
Stajich
Jason E
JE
Dietrich
Fred S
FS
Harrison
Paul M
PM
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005800:Genes, Fungal; D005979:Glutathione Peroxidase; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors; D010802:Phylogeny; D011328:Prions / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D004718:Saccharomycetales / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D010454:Peptide Termination Factors; D011328:Prions; D020543:Proteome; C404807:RNQ1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae