Amino Acid Metabolic Origin as an Evolutionary Influence on Protein Sequence in Yeast

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Amino Acid Metabolic Origin as an Evolutionary Influence on Protein Sequence in Yeast

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dc.contributor.author de Bivort, Benjamin Lovegren
dc.contributor.author Perlstein, Ethan O.
dc.contributor.author Kunes, Samuel M.
dc.contributor.author Schreiber, Stuart L.
dc.date.accessioned 2010-09-30T13:40:13Z
dc.date.issued 2009
dc.identifier.citation de Bivort, Benjamin L., Perlstein, Ethan O. Perlstein, Sam Kunes, and Stuart L. Schreiber. 2009. Amino acid metabolic origin as an evolutionary influence on protein sequence in yeast. Journal of Molecular Evolution 68(5): 490-497. en_US
dc.identifier.issn 0022-2844 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4454163
dc.description.abstract The metabolic cycle of Saccharomyces cerevisiae consists of alternating oxidative (respiration) and reductive (glycolysis) energy-yielding reactions. The intracellular concentrations of amino acid precursors generated by these reactions oscillate accordingly, attaining maximal concentration during the middle of their respective yeast metabolic cycle phases. Typically, the amino acids themselves are most abundant at the end of their precursor’s phase. We show that this metabolic cycling has likely biased the amino acid composition of proteins across the S. cerevisiae genome. In particular, we observed that the metabolic source of amino acids is the single most important source of variation in the amino acid compositions of functionally related proteins and that this signal appears only in (facultative) organisms using both oxidative and reductive metabolism. Periodically expressed proteins are enriched for amino acids generated in the preceding phase of the metabolic cycle. Proteins expressed during the oxidative phase contain more glycolysis-derived amino acids, whereas proteins expressed during the reductive phase contain more respiration-derived amino acids. Rare amino acids (e.g., tryptophan) are greatly overrepresented or underrepresented, relative to the proteomic average, in periodically expressed proteins, whereas common amino acids vary by a few percent. Genome-wide, we infer that 20,000 to 60,000 residues have been modified by this previously unappreciated pressure. This trend is strongest in ancient proteins, suggesting that oscillating endogenous amino acid availability exerted genome-wide selective pressure on protein sequences across evolutionary time.Electronic supplementary material The online version of this article (doi:10.1007/s00239-009-9218-5) contains supplementary material, which is available to authorized users. en_US
dc.description.sponsorship Chemistry and Chemical Biology en_US
dc.language.iso en_US en_US
dc.publisher Springer-Verlag en_US
dc.relation.isversionof doi:10.1007/s00239-009-9218-5 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687519/pdf/ en_US
dash.license OAP
dc.subject amino acid sequence en_US
dc.subject metabolism en_US
dc.subject optimization en_US
dc.subject oxidation en_US
dc.subject protein function en_US
dc.subject reduction en_US
dc.subject yeast metabolic cycle en_US
dc.title Amino Acid Metabolic Origin as an Evolutionary Influence on Protein Sequence in Yeast en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Journal of Molecular Evolution en_US
dash.depositing.author Schreiber, Stuart L.
dc.date.available 2010-09-30T13:40:13Z

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  • FAS Scholarly Articles [6948]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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