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. 2019 Jul 11:6:54.
doi: 10.3389/fmolb.2019.00054. eCollection 2019.

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

Ting-Yi Su  1 , Paul M Harrison  1
Affiliations

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

Ting-Yi Su et al. Front Mol Biosci. .

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.

Keywords: asparagine; disease; evolution; fungi; glutamine; prion; sequence analysis.

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Figures

Figure 1
Figure 1
The fungal levels examined for conservation of prion(-like) proteins from Saccharomyces cerevisiae. (A) A schematic of the three taxonomic levels examined. “WGD” stands for “whole genome duplication.”(B) Conservation values of the different sets of prion-like or prion-forming domains. The abbreviations for the sets are as listed in section Methods. The mean conservation values for prion-forming or prion-like domains are listed along the top of the table, with the values for the whole sequences listed along the left-hand column. The standard deviations are in brackets. The number of coulmns in each sample is indicated (n). They are colour-coded as in part (A). t-Tests were performed to compare the mean conservation values for each set, in the upper diagonal half for the prion(-like) domains and in the lower diagonal for the whole sequences of the same proteins. “NS” means “not significant”.
Figure 2
Figure 2
Individual mean conservation values for prion-forming domains. These are tabulated for each domain, with the top, middle, and bottom thirds colour-coded red, green, and blue, but with the ordering of the first column maintained across the figure. The numerical ranking is also listed for each domain at each level. The domains that are conserved in the same thirds at all levels are in bold italic. There is only one domain that moves between all three thirds of the list (underlined). The standard deviations are in brackets.
Figure 3
Figure 3
Evolutionarily-weighted prion score (EWPS). (A) Scatterplot of the EWPS vs. the Saccharomyces cerevisiae prion score (SCPS) for the prion-forming protein set at the Saccharomycetes level. Only one has an EWPS > SCPS (green point). Seventeen of the domains have EWPS < the lowest value of SCPS for a known prion domain (=35.6 for PIN3). Below the plot is a tabulation of R-values of these correlations for the PFP and PLP sets at the three evolutionary levels. These are all significant at P < 0.000001. The percent sequence identity method for calculating the EWPS has been used, but the difference in results obtained with the bitscore method in all cases is minimal. “NS” stands for “not significant.” (B) Scatterplot of the EWPS vs. the conservation score at the Saccharomycetes level for the prion-like protein set. Below the plot is a tabulation of R-values for the PFP and PLP sets at the three evolutionary levels. The significant P-values are in brackets. (C) Ranking of KPs, PFPs and PLPs relative to each other for evolutionarily-weighted prion score (EWPS). Tabulation of results of Mann-Whitney U-tests for comparison of the EWPS scores of the PFP, PLP and KP sets. Colour coding is as in Figure 1.
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