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    Emergence and evolution of yeast prion and prion-like proteins


    An, Lu and Fitzpatrick, David A. and Harrison, Paul M. (2016) Emergence and evolution of yeast prion and prion-like proteins. BMC Evolutionary Biology, 16 (24). ISSN 1471-2148

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    Abstract

    Background: Prions are transmissible, propagating alternative states of proteins, and are usually made from the fibrillar, beta-sheet-rich assemblies termed amyloid. Prions in the budding yeast Saccharomyces cerevisiae propagate heritable phenotypes, uncover hidden genetic variation, function in large-scale gene regulation, and can act like diseases. Almost all these amyloid prions have asparagine/glutamine-rich (N/Q–rich) domains. Other proteins, that we term here ‘prionogenic amyloid formers’ (PAFs), have been shown to form amyloid in vivo, and to have N/Qrich domains that can propagate heritable states in yeast cells. Also, there are >200 other S.cerevisiae proteins with prion-like N/Q-rich sequence composition. Furthermore, human proteins with such N/Q-rich composition have been linked to the pathomechanisms of neurodegenerative amyloid diseases. Results: Here, we exploit the increasing abundance of complete fungal genomes to examine the ancestry of prions/PAFs and other N/Q-rich proteins across the fungal kingdom. We find distinct evolutionary behavior for Q-rich and N-rich prions/PAFs; those of ancient ancestry (outside the budding yeasts, Saccharomycetes) are Q-rich, whereas N-rich cases arose early in Saccharomycetes evolution. This emergence of N-rich prion/PAFs is linked to a large-scale emergence of N-rich proteins during Saccharomycetes evolution, with Saccharomycetes showing a distinctive trend for population sizes of prion-like proteins that sets them apart from all the other fungi. Conversely, some clades, e.g. Eurotiales, have much fewer N/Q-rich proteins, and in some cases likely lose them en masse, perhaps due to greater amyloid intolerance, although they contain relatively more non-N/Q-rich predicted prions. We find that recent mutational tendencies arising during Saccharomycetes evolution (i.e., increased numbers of N residues and a tendency to form more poly-N tracts), contributed to the expansion/development of the prion phenomenon. Variation in these mutational tendencies in Saccharomycetes is correlated with the population sizes of prion-like proteins, thus implying that selection pressures on N/Q-rich protein sequences against amyloidogenesis are not generally maintained in budding yeasts. Conclusions: These results help to delineate further the limits and origins of N/Q-rich prions, and provide insight as a case study of the evolution of compositionally-defined protein domains.

    Item Type: Article
    Additional Information: © 2016 An et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
    Keywords: Prion; Evolution; Bias; Composition; Bioinformatics; Disease; Mutation; Yeast; Fungi;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7069
    Identification Number: https://doi.org/10.1186/s12862-016-0594-3
    Depositing User: David Fitzpatrick
    Date Deposited: 05 Apr 2016 15:28
    Journal or Publication Title: BMC Evolutionary Biology
    Publisher: BioMed Central
    Refereed: Yes
    URI:

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