Evolutionary systems biology of amino acid biosynthetic cost in yeast

• Published in: PloS one Vol. 5; no. 8; p. e11935
• Main Authors: Barton, Michael D, Delneri, Daniela, Oliver, Stephen G, Rattray, Magnus, Bergman, Casey M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-08-2010; Public Library of Science (PLoS)
• Subjects: Amino Acid Substitution; Amino acid synthesis; Amino acids; Amino Acids - biosynthesis; Ammonia - metabolism; Atomic properties; Bacterial proteins; Baking yeast; Bias; Biological effects; Biological evolution; Biological Transport; Biology; Biosynthesis; Codons; Computational Biology/Comparative Sequence Analysis; Computational Biology/Evolutionary Modeling; Computational Biology/Systems Biology; Costs; E coli; Economic aspects; Environmental changes; Environmental conditions; Escherichia coli - genetics; Escherichia coli - metabolism; Evolution; Evolution, Molecular; Fitness; Food; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene expression; Gene Expression Profiling; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Functional Genomics; Genetics and Genomics/Microbial Evolution and Genomics; Genomes; Genomics; Glucose - metabolism; Hypotheses; Life sciences; Linear programming; Metabolism; Metabolites; Molecular biology; Molecular weight; Natural selection; Ontology; Phylogenetics; Physiological aspects; Proteins; Proteome - genetics; Proteome - metabolism; Reproductive fitness; RNA, Transfer - genetics; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Shadow prices; Structure-function relationships; Sulfates - metabolism; Systems Biology; Transcription; Transfer RNA; Trends; tRNA; United States > US; Kentucky
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0011935

Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental conditions, we conclude that a systems approach is necessary to unravel the full effects of amino acid biosynthetic cost in complex biological systems.