Molecular population genetics and evolution of a prion-like protein in Saccharomyces cerevisiae

The prion-like behavior of Sup35p, the eRF3 homolog in the yeast Saccharomy ces cerevisiae, mediates the activity of the Cytoplasmic nonsense suppresso r known as [PSI+]. Sup35p is divided into three regions of distinct functio n. The N-terminal and middle (M) regions are required for the induction and propagation of [PSI+] but are not necessary for translation termination or cell viability. The C-terminal region encompasses the termination function . The existence of the N-terminal region in SUP35 homologs of other fungi h as led some to suggest that this region has an adaptive function separate f rom translation termination. To examine this hypothesis, we sequenced porti ons of SUP35 in 21 strains of S. cerevisiae, including 13 clinical isolates . We analyzed nucleotide polymorphism within this species and compared it t o sequence divergence from a sister species, S. paradoxus. The N domain of Sup35p is highly conserved in amino acid sequence and is highly biased in c odon usage toward preferred codons. Amino acid changes are under weak purif ying selection based on a quantitative analysis of polymorphism and diverge nce. We also conclude that the clinical strains of S. cerevisiae are not re cently derived and that outcrossing between strains in S. cerevisiae may be relatively rare in nature.