Linking Post-Translational Modifications and Variation of Phenotypic Traits

Abstract

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 and isoforms of alcoholic fermentation, metabolic traits, and growth-related traits in Saccharomyces cerevisiae. Although 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 posttranslational modifications in the diversity of metabolic and life-history traits. Molecular & Cellular Proteomics 12: 10.1074/mcp.M112.024349, 720 -735, 2013.The key problem in understanding genotype-phenotype relationships is the complexity arising from multiple levels of cellular functioning. Among them, metabolic networks involve series of interconnected chemical reactions catalyzed by enzymes, allowing the transformation of input substrates into intermediate or final metabolites. These networks play an essential role in an organism's growth, reproduction, and ability to maintain cell integrity and to respond to environmental changes (1, 2). The metabolic fluxes, as well as the metabolite concentrations, are governed by the activity of the enzymes, which depends on three types of factors: kinetic parameters, enzyme abundance, and activation state of the enzyme. The kinetic parameters are determined by the sequence and the three-dimensional structure of the protein (3). The abundance of the enzymes is the result of numerous molecular processes taking place from the transcriptional to the translational level, including epigenetic modifications of the DNA and chromatin (4), transcriptional regulation by transcription factors (5), mRNA capping and splicing and small RNA regulation (6), protein turnover (7), etc. The enzyme activation state is primarily because of post-translational modifications of the native protein, themselves highly regulated (8, 9). Other mechanisms involved in enzyme activity are proteinprotein interactions and allosteric regulation, such mechanisms being sometimes mediated through post-translational modifications (10, 11). The resulting isoforms can display differences in activity, affinity for partners (protein or effectors), and stability (12). The most studied modification is the reversibl...

Heterosis is a systemic property emerging from nonlinear genotype-phenotype relationships: evidence fromin vitrogenetics and computer simulations

“…Crowding [151] and energy cost [152, 153] create constraints on the total content of cell components. For instance in yeast, Albertin et al [79] showed that the enzymatic pool allocated to the glycolysis, glycerol, acetate, and ethanol pathways was invariant regardless of the culture medium and strain considered. When some proteins are overexpressed, this constancy can sometimes lead to burden effects, which causes a decline in flux [154], as we found under constrained E tot .…”

“…For the optimum-centered distributions, the means were µ = 15.768 mg.L −1 , µ = 25.162 mg.L −1 , µ = 59.497 mg.L −1 and µ = 1.473 mg.L −1 for PGI, PFK, FBA and TPI, respectively, computed from Eq 7. In all cases we varied the coefficients of variation from c v = 0.1 to c v = 1.2, within the range of observed c v ’s for these enzymes [79]. The shape and scale parameters of the gamma distributions were respectively and .…”

A Systems Approach to Elucidate Heterosis of Protein Abundances in Yeast

“…To explain the peculiar behavior of these proteins, we assume that factors other than TFs are involved in heterosis for protein abundance as, for example, posttranslational modifications, that were recently shown to be related to the variations of phenotypic traits (86).…”

A systems genetics approach reveals environment-dependent associations between SNPs, protein co-expression and drought-related traits in maize

“…Yet, proteins are particularly relevant molecular components to link genotype to phenotype. Due to the buffering of transcriptional variations and to the role of post-translational regulations in phenotypes construction, proteins are indeed expected to be more highly related to end-point phenotypes than transcripts (Foss et al 2011; Battle et al 2015; Chick et al 2016; Albertin et al 2013; Vogel and Marcotte 2012).…”