title: Evolutionary systems biology of amino acid biosynthetic cost in yeast.
abstract: 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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Barton
authors.forename: Daniela
authors.initials: D
authors.lastname: Delneri
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oliver
authors.forename: Magnus
authors.initials: M
authors.lastname: Rattray
authors.forename: Casey M
authors.initials: CM
authors.lastname: Bergman
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000096:biosynthesis*; D000641:Ammonia / Q000378:metabolism; D001692:Biological Transport; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005502:Food; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D049490:Systems Biology
chemical_list: D000596:Amino Acids; D005656:Fungal Proteins; D020543:Proteome; D013431:Sulfates; D000641:Ammonia; D012343:RNA, Transfer; D005947:Glucose
references.citation: J Mol Evol. 2003 Feb;56(2):151-61
references.pmid: 12574861
references.citation: Nature. 2003 Oct 16;425(6959):737-41
references.pmid: 14562106
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19302-7
references.pmid: 17159141
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D577-81
references.pmid: 17982175
references.citation: PLoS Comput Biol. 2007 Mar 23;3(3):e57
references.pmid: 17381238
references.citation: Genetics. 2003 Aug;164(4):1291-303
references.pmid: 12930740
references.citation: Nature. 2006 Aug 24;442(7105):E11-2; discussion E12
references.pmid: 16929253
references.citation: Mol Biol Evol. 1998 Jun;15(6):774-6
references.pmid: 9615459
references.citation: Science. 1997 Oct 24;278(5338):680-6
references.pmid: 9381177
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5483-8
references.pmid: 15800036
references.citation: Appl Environ Microbiol. 1993 Aug;59(8):2465-73
references.pmid: 8368835
references.citation: Mol Syst Biol. 2007;3:121
references.pmid: 17593909
references.citation: Nat Protoc. 2007;2(3):727-38
references.pmid: 17406635
references.citation: J Mol Evol. 2007 May;64(5):558-71
references.pmid: 17476453
references.citation: J Mol Biol. 1982 Jul 15;158(4):573-97
references.pmid: 6750137
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13134-9
references.pmid: 14578455
references.citation: Proc Natl Acad Sci U S A. 2005 May 24;102(21):7695-700
references.pmid: 15897462
references.citation: Mol Biol Evol. 2006 Sep;23(9):1670-80
references.pmid: 16754641
references.citation: Mol Biol Evol. 2001 May;18(5):691-9
references.pmid: 11319253
references.citation: Genome Res. 2004 Jul;14(7):1298-309
references.pmid: 15197165
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15112-7
references.pmid: 12415116
references.citation: Science. 1974 Sep 6;185(4154):862-4
references.pmid: 4843792
references.citation: Mol Biol Cell. 2005 May;16(5):2503-17
references.pmid: 15758028
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3695-700
references.pmid: 11904428
references.citation: Genome Biol. 2003;4(9):R54
references.pmid: 12952533
references.citation: J Mol Evol. 2008 Dec;67(6):621-30
references.pmid: 18937004
references.citation: Mol Biol Evol. 2004 Jan;21(1):108-16
references.pmid: 14595100
references.citation: Mol Biol Evol. 2005 Jun;22(6):1365-74
references.pmid: 15758206
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: Bioinformatics. 2007 May 15;23(10):1258-64
references.pmid: 17344237
references.citation: Nucleic Acids Res. 2003 Apr 15;31(8):2242-51
references.pmid: 12682375
references.citation: Brief Bioinform. 2006 Jun;7(2):140-50
references.pmid: 16772264
references.citation: J Biol. 2007;6(2):4
references.pmid: 17439666
references.citation: Nat Rev Genet. 2006 May;7(5):337-48
references.pmid: 16619049
references.citation: Mol Syst Biol. 2007;3:119
references.pmid: 17625511