Linking Post-Translational Modifications and Variation of Phenotypic Traits

CNRS, France
Molecular & Cellular Proteomics (Impact Factor: 6.56). 12/2012; 12(3). DOI: 10.1074/mcp.M112.024349
Source: PubMed


Enzymes can be post-translationally modified, leading to isoforms with different properties. The phenotypic consequences of the quantitative variability of isoforms have never been studied. We used quantitative proteomics to dissect the relationships between the abundances of the enzymes/isoforms of alcoholic fermentation, metabolic traits and growth-related traits in Saccharomyces cerevisiae. While the enzymatic pool allocated to the fermentation proteome was constant over the culture media and the strains considered, there was variation in abundance of individual enzymes and sometimes much more of their isoforms, which suggests the existence of selective constraints on total protein abundance and trade-offs between isoforms. Variations in abundance of some isoforms were significantly associated to metabolic traits and growth-related traits. In particular, cell size and maximum population size were highly correlated to the degree of N-terminal acetylation of the alcohol dehydrogenase. The fermentation proteome was found to be shaped by human selection, through the differential targeting of a few isoforms for each food-processing origin of strains. These results highlight the importance of post-translational modifications in the diversity of metabolic and life-history traits.

Download full-text


Available from: Warren Albertin
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Saccharomyces cerevisiae and S. uvarum are two domesticated species of the Saccharomyces sensu stricto clade that diverged around 100 million years ago after a whole genome duplication. Both have retained many duplicated genes associated with glucose fermentation and are characterized by the ability to achieve grape juice fermentation. Nevertheless, these two species differ for many other traits, indicating that they underwent different evolutionary histories. To determine how the evolutionary histories of S. cerevisiae and S. uvarum are mirrored on the proteome, we analyzed the genetic variability of the proteomes of domesticated strains of these two species by quantitative mass-spectrometry. Overall, 445 proteins were quantified. Massive variations of protein abundances were found, that clearly differentiated the two species. Abundance variations in specific metabolic pathways could be related to phenotypic traits known to discriminate the two species. In addition, proteins encoded by duplicated genes were shown to be differently recruited in each species. Comparing the strain differentiation based on the proteome variability to those based on the phenotypic and genetic variations further revealed that the strains of S. uvarum and some strains of S. cerevisiae displayed similar fermentative performances in spite of strong proteomic and genomic differences. Altogether, these results indicate that the ability of S. cerevisae and S. uvarum to complete grape juice fermentation arose through different evolutionary roads, involving different metabolic pathways and duplicated genes.
    Full-text · Article · Mar 2013 · Molecular Biology and Evolution
  • Source

    Full-text · Dataset · Dec 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Amino-terminal acetylation is among the most ubiquitous of protein modifications in eukaryotes. Although loss of N-terminal acetylation is associated with many abnormalities, the molecular basis of these effects is known for only a few cases, where acetylation of single factors has been linked to binding avidity or metabolic stability. In contrast, the impact of N-terminal acetylation for the majority of the proteome, and its combinatorial contributions to phenotypes, are unknown. Here, by studying the yeast prion [PSI(+)], an amyloid of the Sup35 protein, we show that loss of N-terminal acetylation promotes general protein misfolding, a redeployment of chaperones to these substrates, and a corresponding stress response. These proteostasis changes, combined with the decreased stability of unacetylated Sup35 amyloid, reduce the size of prion aggregates and reverse their phenotypic consequences. Thus, loss of N-terminal acetylation, and its previously unanticipated role in protein biogenesis, globally resculpts the proteome to create a unique phenotype.
    Full-text · Article · Jul 2014 · Nature Communications
Show more