Conservation of Prion-Like Composition and Sequence in Prion-Formers and Prion-Like Proteins of Saccharomyces cerevisiae

Ting-Yi Su,Paul M Harrison

doi:10.3389/fmolb.2019.00054

Abstract

Prions in eukaryotes have been linked to diseases, evolutionary capacitance, large-scale genetic control, and long-term memory formation. Prion formation and propagation have been studied extensively in the budding yeast Saccharomyces cerevisiae. Here, we have analysed the conservation of sequence and of prion-like composition for prion-forming proteins and for other prion-like proteins from S. cerevisiae, across three evolutionary levels. We discover that prion-like status is well-conserved for about half the set of prion-formers at the Saccharomycetes level, and that prion-forming domains evolve more quickly as sequences than other prion-like domains do. Such increased mutation rates may be linked to the acquisition of functional roles for prion-forming domains during the evolutionary epoch of Saccharomycetes. Domain scores for prion-like composition in S. cerevisiae are strongly correlated with scores for such composition weighted evolutionarily over the dozens of fungal species examined, indicating conservation of such prion-like status. Examples of notable prion-like proteins that are highly conserved both in sequence and prion-like composition are discussed.

Highlights

Prions are proteinaceous infectious particles that were originally identified as the causative agents of devastating neurological diseases in mammals
For proteins with more evidence of prion-forming ability, the sequences have faster evolutionary rates. Such increased mutation rates may be linked to the acquisition of functional roles for prion-forming domains during the evolutionary epoch of Saccharomycetes
Out of the large “test set” of prion-like N/Q-rich domains that has formed during Saccharomycetes evolution (An and Harrison, 2016), we suggest that those that have become functional have mutated more quickly

Summary

Introduction

Prions are proteinaceous infectious particles that were originally identified as the causative agents (made from the prion protein PrP) of devastating neurological diseases in mammals. In budding yeast (Saccharomyces cerevisiae), propagation of these alternative states can be sustained during budding, mating, and artificial laboratory protocols. Such yeast prions have been linked to diverse phenomena including evolutionary capacitance, disease-like states, and large-scale genetic control. The first well-characterized yeast prions, that underlie the [PSI+] and [URE3] prions, are propagating amyloids of the proteins Sup35p and Ure2p, respectively. [PSI+] prion formation reduces translation termination efficiency and increases non-sense-codon read-through levels (Cox, 1965; Shorter and Lindquist, 2005). This read-through has been shown to have a potential

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