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. 2003 Aug;164(4):1291–1303. doi: 10.1093/genetics/164.4.1291

Translational selection and yeast proteome evolution.

Hiroshi Akashi 1
PMCID: PMC1462678  PMID: 12930740

Abstract

The primary structures of peptides may be adapted for efficient synthesis as well as proper function. Here, the Saccharomyces cerevisiae genome sequence, DNA microarray expression data, tRNA gene numbers, and functional categorizations of proteins are employed to determine whether the amino acid composition of peptides reflects natural selection to optimize the speed and accuracy of translation. Strong relationships between synonymous codon usage bias and estimates of transcript abundance suggest that DNA array data serve as adequate predictors of translation rates. Amino acid usage also shows striking relationships with expression levels. Stronger correlations between tRNA concentrations and amino acid abundances among highly expressed proteins than among less abundant proteins support adaptation of both tRNA abundances and amino acid usage to enhance the speed and accuracy of protein synthesis. Natural selection for efficient synthesis appears to also favor shorter proteins as a function of their expression levels. Comparisons restricted to proteins within functional classes are employed to control for differences in amino acid composition and protein size that reflect differences in the functional requirements of proteins expressed at different levels.

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Selected References

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  1. Akashi H. Gene expression and molecular evolution. Curr Opin Genet Dev. 2001 Dec;11(6):660–666. doi: 10.1016/s0959-437x(00)00250-1. [DOI] [PubMed] [Google Scholar]
  2. Akashi H. Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination. Genetics. 1999 Jan;151(1):221–238. doi: 10.1093/genetics/151.1.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akashi H. Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. Genetics. 1995 Feb;139(2):1067–1076. doi: 10.1093/genetics/139.2.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Akashi H. Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. Genetics. 1996 Nov;144(3):1297–1307. doi: 10.1093/genetics/144.3.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Akashi Hiroshi, Gojobori Takashi. Metabolic efficiency and amino acid composition in the proteomes of Escherichia coli and Bacillus subtilis. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3695–3700. doi: 10.1073/pnas.062526999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  7. Andersson S. G., Kurland C. G. Codon preferences in free-living microorganisms. Microbiol Rev. 1990 Jun;54(2):198–210. doi: 10.1128/mr.54.2.198-210.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ares M., Jr, Grate L., Pauling M. H. A handful of intron-containing genes produces the lion's share of yeast mRNA. RNA. 1999 Sep;5(9):1138–1139. doi: 10.1017/s1355838299991379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Betancourt Andrea J., Presgraves Daven C. Linkage limits the power of natural selection in Drosophila. Proc Natl Acad Sci U S A. 2002 Oct 7;99(21):13616–13620. doi: 10.1073/pnas.212277199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bin T., McCrosky L., Kulshreshtha A. K., Hem S. L. Adsorption of esters of p-hydroxybenzoic acid by filter membranes: mechanism and effect of formulation and processing parameters. Pharm Dev Technol. 2000;5(1):95–104. doi: 10.1081/pdt-100100524. [DOI] [PubMed] [Google Scholar]
  11. Birdsell John A. Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution. Mol Biol Evol. 2002 Jul;19(7):1181–1197. doi: 10.1093/oxfordjournals.molbev.a004176. [DOI] [PubMed] [Google Scholar]
  12. Castillo-Davis Cristian I., Mekhedov Sergei L., Hartl Daniel L., Koonin Eugene V., Kondrashov Fyodor A. Selection for short introns in highly expressed genes. Nat Genet. 2002 Jul 22;31(4):415–418. doi: 10.1038/ng940. [DOI] [PubMed] [Google Scholar]
  13. Costanzo M. C., Hogan J. D., Cusick M. E., Davis B. P., Fancher A. M., Hodges P. E., Kondu P., Lengieza C., Lew-Smith J. E., Lingner C. The yeast proteome database (YPD) and Caenorhabditis elegans proteome database (WormPD): comprehensive resources for the organization and comparison of model organism protein information. Nucleic Acids Res. 2000 Jan 1;28(1):73–76. doi: 10.1093/nar/28.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Craig C. L., Riekel C., Herberstein M. E., Weber R. S., Kaplan D., Pierce N. E. Evidence for diet effects on the composition of silk proteins produced by spiders. Mol Biol Evol. 2000 Dec;17(12):1904–1913. doi: 10.1093/oxfordjournals.molbev.a026292. [DOI] [PubMed] [Google Scholar]
  15. Craig C. L., Weber R. S. Selection costs of amino acid substitutions in ColE1 and ColIa gene clusters harbored by Escherichia coli. Mol Biol Evol. 1998 Jun;15(6):774–776. doi: 10.1093/oxfordjournals.molbev.a025981. [DOI] [PubMed] [Google Scholar]
  16. Crick F. H., Brenner S., Klug A., Pieczenik G. A speculation on the origin of protein synthesis. Orig Life. 1976 Dec;7(4):389–397. doi: 10.1007/BF00927934. [DOI] [PubMed] [Google Scholar]
  17. Datta A., Jinks-Robertson S. Association of increased spontaneous mutation rates with high levels of transcription in yeast. Science. 1995 Jun 16;268(5217):1616–1619. doi: 10.1126/science.7777859. [DOI] [PubMed] [Google Scholar]
  18. Davis C. A., Grate L., Spingola M., Ares M., Jr Test of intron predictions reveals novel splice sites, alternatively spliced mRNAs and new introns in meiotically regulated genes of yeast. Nucleic Acids Res. 2000 Apr 15;28(8):1700–1706. doi: 10.1093/nar/28.8.1700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dufton M. J. Genetic code synonym quotas and amino acid complexity: cutting the cost of proteins? J Theor Biol. 1997 Jul 21;187(2):165–173. doi: 10.1006/jtbi.1997.0443. [DOI] [PubMed] [Google Scholar]
  20. Duret L., Mouchiroud D. Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Mol Biol Evol. 2000 Jan;17(1):68–74. doi: 10.1093/oxfordjournals.molbev.a026239. [DOI] [PubMed] [Google Scholar]
  21. Duret L., Mouchiroud D. Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4482–4487. doi: 10.1073/pnas.96.8.4482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Duret L. tRNA gene number and codon usage in the C. elegans genome are co-adapted for optimal translation of highly expressed genes. Trends Genet. 2000 Jul;16(7):287–289. doi: 10.1016/s0168-9525(00)02041-2. [DOI] [PubMed] [Google Scholar]
  23. Duret Laurent. Evolution of synonymous codon usage in metazoans. Curr Opin Genet Dev. 2002 Dec;12(6):640–649. doi: 10.1016/s0959-437x(02)00353-2. [DOI] [PubMed] [Google Scholar]
  24. Farabaugh P. J. Translational frameshifting: implications for the mechanism of translational frame maintenance. Prog Nucleic Acid Res Mol Biol. 2000;64:131–170. doi: 10.1016/s0079-6603(00)64004-7. [DOI] [PubMed] [Google Scholar]
  25. Francino M. P., Chao L., Riley M. A., Ochman H. Asymmetries generated by transcription-coupled repair in enterobacterial genes. Science. 1996 Apr 5;272(5258):107–109. doi: 10.1126/science.272.5258.107. [DOI] [PubMed] [Google Scholar]
  26. Futcher B., Latter G. I., Monardo P., McLaughlin C. S., Garrels J. I. A sampling of the yeast proteome. Mol Cell Biol. 1999 Nov;19(11):7357–7368. doi: 10.1128/mcb.19.11.7357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Garat B., Musto H. Trends of amino acid usage in the proteins from the unicellular parasite Giardia lamblia. Biochem Biophys Res Commun. 2000 Dec 29;279(3):996–1000. doi: 10.1006/bbrc.2000.4051. [DOI] [PubMed] [Google Scholar]
  28. Garel J. P. Functional adaptation of tRNA population. J Theor Biol. 1974 Jan;43(1):211–225. doi: 10.1016/s0022-5193(74)80054-8. [DOI] [PubMed] [Google Scholar]
  29. Gerton J. L., DeRisi J., Shroff R., Lichten M., Brown P. O., Petes T. D. Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11383–11390. doi: 10.1073/pnas.97.21.11383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Goffeau A., Barrell B. G., Bussey H., Davis R. W., Dujon B., Feldmann H., Galibert F., Hoheisel J. D., Jacq C., Johnston M. Life with 6000 genes. Science. 1996 Oct 25;274(5287):546, 563-7. doi: 10.1126/science.274.5287.546. [DOI] [PubMed] [Google Scholar]
  31. Grosjean H., Fiers W. Preferential codon usage in prokaryotic genes: the optimal codon-anticodon interaction energy and the selective codon usage in efficiently expressed genes. Gene. 1982 Jun;18(3):199–209. doi: 10.1016/0378-1119(82)90157-3. [DOI] [PubMed] [Google Scholar]
  32. Grosjean H., Sankoff D., Jou W. M., Fiers W., Cedergren R. J. Bacteriophage MS2 RNA: a correlation between the stability of the codon: anticodon interaction and the choice of code words. J Mol Evol. 1978 Dec 29;12(2):113–119. doi: 10.1007/BF01733262. [DOI] [PubMed] [Google Scholar]
  33. Gutiérrez G., Márquez L., Marín A. Preference for guanosine at first codon position in highly expressed Escherichia coli genes. A relationship with translational efficiency. Nucleic Acids Res. 1996 Jul 1;24(13):2525–2527. doi: 10.1093/nar/24.13.2525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Hatfield D., Varricchio F., Rice M., Forget B. G. The aminoacyl-tRNA population of human reticulocytes. J Biol Chem. 1982 Mar 25;257(6):3183–3188. [PubMed] [Google Scholar]
  35. Holstege F. C., Jennings E. G., Wyrick J. J., Lee T. I., Hengartner C. J., Green M. R., Golub T. R., Lander E. S., Young R. A. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717–728. doi: 10.1016/s0092-8674(00)81641-4. [DOI] [PubMed] [Google Scholar]
  36. Iida K., Akashi H. A test of translational selection at 'silent' sites in the human genome: base composition comparisons in alternatively spliced genes. Gene. 2000 Dec 30;261(1):93–105. doi: 10.1016/s0378-1119(00)00482-0. [DOI] [PubMed] [Google Scholar]
  37. Ikemura T. Correlation between the abundance of yeast transfer RNAs and the occurrence of the respective codons in protein genes. Differences in synonymous codon choice patterns of yeast and Escherichia coli with reference to the abundance of isoaccepting transfer RNAs. J Mol Biol. 1982 Jul 15;158(4):573–597. doi: 10.1016/0022-2836(82)90250-9. [DOI] [PubMed] [Google Scholar]
  38. Jansen R., Gerstein M. Analysis of the yeast transcriptome with structural and functional categories: characterizing highly expressed proteins. Nucleic Acids Res. 2000 Mar 15;28(6):1481–1488. doi: 10.1093/nar/28.6.1481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kanaya S., Yamada Y., Kudo Y., Ikemura T. Studies of codon usage and tRNA genes of 18 unicellular organisms and quantification of Bacillus subtilis tRNAs: gene expression level and species-specific diversity of codon usage based on multivariate analysis. Gene. 1999 Sep 30;238(1):143–155. doi: 10.1016/s0378-1119(99)00225-5. [DOI] [PubMed] [Google Scholar]
  40. Karlin S., Bucher P. Correlation analysis of amino acid usage in protein classes. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12165–12169. doi: 10.1073/pnas.89.24.12165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Kliman R. M., Hey J. The effects of mutation and natural selection on codon bias in the genes of Drosophila. Genetics. 1994 Aug;137(4):1049–1056. doi: 10.1093/genetics/137.4.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lobry J. R., Gautier C. Hydrophobicity, expressivity and aromaticity are the major trends of amino-acid usage in 999 Escherichia coli chromosome-encoded genes. Nucleic Acids Res. 1994 Aug 11;22(15):3174–3180. doi: 10.1093/nar/22.15.3174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lopez P. J., Séraphin B. Genomic-scale quantitative analysis of yeast pre-mRNA splicing: implications for splice-site recognition. RNA. 1999 Sep;5(9):1135–1137. doi: 10.1017/s135583829999091x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Marais G., Mouchiroud D., Duret L. Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes. Proc Natl Acad Sci U S A. 2001 Apr 24;98(10):5688–5692. doi: 10.1073/pnas.091427698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mazel D., Marlière P. Adaptive eradication of methionine and cysteine from cyanobacterial light-harvesting proteins. Nature. 1989 Sep 21;341(6239):245–248. doi: 10.1038/341245a0. [DOI] [PubMed] [Google Scholar]
  46. Morey N. J., Greene C. N., Jinks-Robertson S. Genetic analysis of transcription-associated mutation in Saccharomyces cerevisiae. Genetics. 2000 Jan;154(1):109–120. doi: 10.1093/genetics/154.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Moriyama E. N., Powell J. R. Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces cerevisiae and Escherichia coli. Nucleic Acids Res. 1998 Jul 1;26(13):3188–3193. doi: 10.1093/nar/26.13.3188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Morton B. R., So B. G. Codon usage in plastid genes is correlated with context, position within the gene, and amino acid content. J Mol Evol. 2000 Feb;50(2):184–193. doi: 10.1007/s002399910020. [DOI] [PubMed] [Google Scholar]
  49. Nassar R. F., Cook R. D. Non-randomness of nucleotide bases in mRNA codons. Genet Res. 1976 Jun;27(3):353–362. doi: 10.1017/s0016672300016578. [DOI] [PubMed] [Google Scholar]
  50. Ogle J. M., Brodersen D. E., Clemons W. M., Jr, Tarry M. J., Carter A. P., Ramakrishnan V. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science. 2001 May 4;292(5518):897–902. doi: 10.1126/science.1060612. [DOI] [PubMed] [Google Scholar]
  51. Palacios Carmen, Wernegreen Jennifer J. A strong effect of AT mutational bias on amino acid usage in Buchnera is mitigated at high-expression genes. Mol Biol Evol. 2002 Sep;19(9):1575–1584. doi: 10.1093/oxfordjournals.molbev.a004219. [DOI] [PubMed] [Google Scholar]
  52. Percudani R., Ottonello S. Selection at the wobble position of codons read by the same tRNA in Saccharomyces cerevisiae. Mol Biol Evol. 1999 Dec;16(12):1752–1762. doi: 10.1093/oxfordjournals.molbev.a026087. [DOI] [PubMed] [Google Scholar]
  53. Percudani R., Pavesi A., Ottonello S. Transfer RNA gene redundancy and translational selection in Saccharomyces cerevisiae. J Mol Biol. 1997 May 2;268(2):322–330. doi: 10.1006/jmbi.1997.0942. [DOI] [PubMed] [Google Scholar]
  54. Percudani R. Restricted wobble rules for eukaryotic genomes. Trends Genet. 2001 Mar;17(3):133–135. doi: 10.1016/s0168-9525(00)02208-3. [DOI] [PubMed] [Google Scholar]
  55. Precup J., Parker J. Missense misreading of asparagine codons as a function of codon identity and context. J Biol Chem. 1987 Aug 15;262(23):11351–11355. [PubMed] [Google Scholar]
  56. Pál C., Papp B., Hurst L. D. Does the recombination rate affect the efficiency of purifying selection? The yeast genome provides a partial answer. Mol Biol Evol. 2001 Dec;18(12):2323–2326. doi: 10.1093/oxfordjournals.molbev.a003779. [DOI] [PubMed] [Google Scholar]
  57. Richmond R. C. Non-Darwinian evolution: a critique. Nature. 1970 Mar 14;225(5237):1025–1028. doi: 10.1038/2251025a0. [DOI] [PubMed] [Google Scholar]
  58. Robinson M., Lilley R., Little S., Emtage J. S., Yarranton G., Stephens P., Millican A., Eaton M., Humphreys G. Codon usage can affect efficiency of translation of genes in Escherichia coli. Nucleic Acids Res. 1984 Sep 11;12(17):6663–6671. doi: 10.1093/nar/12.17.6663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rodnina M. V., Wintermeyer W. Ribosome fidelity: tRNA discrimination, proofreading and induced fit. Trends Biochem Sci. 2001 Feb;26(2):124–130. doi: 10.1016/s0968-0004(00)01737-0. [DOI] [PubMed] [Google Scholar]
  60. Sharp P. M., Cowe E. Synonymous codon usage in Saccharomyces cerevisiae. Yeast. 1991 Oct;7(7):657–678. doi: 10.1002/yea.320070702. [DOI] [PubMed] [Google Scholar]
  61. Sharp P. M., Stenico M., Peden J. F., Lloyd A. T. Codon usage: mutational bias, translational selection, or both? Biochem Soc Trans. 1993 Nov;21(4):835–841. doi: 10.1042/bst0210835. [DOI] [PubMed] [Google Scholar]
  62. Sharp P. M., Tuohy T. M., Mosurski K. R. Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res. 1986 Jul 11;14(13):5125–5143. doi: 10.1093/nar/14.13.5125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Shpaer E. G. Amino acid composition is correlated with protein abundance in Escherichia coli: can this be due to optimization of translational efficiency? Protein Seq Data Anal. 1989 Feb;2(2):107–110. [PubMed] [Google Scholar]
  64. Sørensen M. A., Kurland C. G., Pedersen S. Codon usage determines translation rate in Escherichia coli. J Mol Biol. 1989 May 20;207(2):365–377. doi: 10.1016/0022-2836(89)90260-x. [DOI] [PubMed] [Google Scholar]
  65. Trifonov E. N. Recognition of correct reading frame by the ribosome. Biochimie. 1992 Apr;74(4):357–362. doi: 10.1016/0300-9084(92)90113-S. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Trifonov E. N., Sussman J. L. The pitch of chromatin DNA is reflected in its nucleotide sequence. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3816–3820. doi: 10.1073/pnas.77.7.3816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Trifonov E. N. Translation framing code and frame-monitoring mechanism as suggested by the analysis of mRNA and 16 S rRNA nucleotide sequences. J Mol Biol. 1987 Apr 20;194(4):643–652. doi: 10.1016/0022-2836(87)90241-5. [DOI] [PubMed] [Google Scholar]
  68. Varenne S., Buc J., Lloubes R., Lazdunski C. Translation is a non-uniform process. Effect of tRNA availability on the rate of elongation of nascent polypeptide chains. J Mol Biol. 1984 Dec 15;180(3):549–576. doi: 10.1016/0022-2836(84)90027-5. [DOI] [PubMed] [Google Scholar]
  69. Warner J. R. The economics of ribosome biosynthesis in yeast. Trends Biochem Sci. 1999 Nov;24(11):437–440. doi: 10.1016/s0968-0004(99)01460-7. [DOI] [PubMed] [Google Scholar]
  70. Wootton J. C., Federhen S. Analysis of compositionally biased regions in sequence databases. Methods Enzymol. 1996;266:554–571. doi: 10.1016/s0076-6879(96)66035-2. [DOI] [PubMed] [Google Scholar]
  71. Wright Stephen I., Lauga Beatrice, Charlesworth Deborah. Rates and patterns of molecular evolution in inbred and outbred Arabidopsis. Mol Biol Evol. 2002 Sep;19(9):1407–1420. doi: 10.1093/oxfordjournals.molbev.a004204. [DOI] [PubMed] [Google Scholar]
  72. Yamao F., Andachi Y., Muto A., Ikemura T., Osawa S. Levels of tRNAs in bacterial cells as affected by amino acid usage in proteins. Nucleic Acids Res. 1991 Nov 25;19(22):6119–6122. doi: 10.1093/nar/19.22.6119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Zavala Alejandro, Naya Hugo, Romero Héctor, Musto Héctor. Trends in codon and amino acid usage in Thermotoga maritima. J Mol Evol. 2002 May;54(5):563–568. doi: 10.1007/s00239-001-0040-y. [DOI] [PubMed] [Google Scholar]

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