Evolution of budding yeast prion-determinant sequences across diverse fungi

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Mycology

Background:

• Prions are self-replicating protein states, with four known cytoplasmic elements ([PSI+], [URE3], [RNQ+], [NU+]) in Saccharomyces cerevisiae.
• Prion formation, particularly [PSI+], may reveal hidden genetic variation.

Purpose of the Study:

• To analyze the evolutionary dynamics of prion-determinant (PD) domains across 21 fungal species.
• To investigate compositional biases, repeats, and substitution rates within these PD domains.

Main Methods:

• Comparative genomic analysis of prion-determinant domains across 21 fungal species.
• Assessment of compositional biases (e.g., Q/N bias), repeat content, and substitution rates.
• Phylogenetic analysis to infer evolutionary constraints and dynamics.

Main Results:

• All four PD domains ([PSI+], [URE3], [RNQ+], [NU+]) show evidence of evolutionary constraint, but with distinct dynamics.
• The Q/N bias in [PSI+] is conserved across fungal clades diverging over a billion years, with purifying selection in Saccharomyces species.
• Prion-associated repeats are rare in other proteins, but Q/N bias correlates with local homology to these repeats.
• The [URE3] PD domain is unique to Hemiascomycota, exhibiting both purifying selection and inter-clade bias changes.
• Hundreds of yeast-prion-like domains were identified across proteomes, with fewer in fission yeast.

Conclusions:

• The study provides strong evidence for the functional significance of yeast prions through their conserved evolutionary patterns.
• Each prion-determinant domain possesses unique evolutionary trajectories, highlighting specialized roles.
• The deep evolutionary conservation of Q/N bias in Sup35p (the [PSI+] determinant) is a notable finding, shared by few other proteins.