Evolution of budding yeast prion-determinant sequences across diverse fungi.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Harrison, LB; Yu, Z; Stajich, JE; Dietrich, FS; Harrison, PM

Published Date

  • April 20, 2007

Published In

Volume / Issue

  • 368 / 1

Start / End Page

  • 273 - 282

PubMed ID

  • 17320905

International Standard Serial Number (ISSN)

  • 0022-2836

Digital Object Identifier (DOI)

  • 10.1016/j.jmb.2007.01.070


  • eng

Conference Location

  • Netherlands