{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:05:04Z","timestamp":1776693904679,"version":"3.51.2"},"reference-count":46,"publisher":"Proceedings of the National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,3,19]]},"abstract":"<jats:p>\n            Biosynthesis of an\n            <jats:italic>Escherichia coli<\/jats:italic>\n            cell, with organic compounds as sources of energy and carbon, requires approximately 20 to 60 billion high-energy phosphate bonds [Stouthamer, A. H. (1973)\n            <jats:italic>Antonie van Leeuwenhoek<\/jats:italic>\n            39, 545\u2013565]. A substantial fraction of this energy budget is devoted to biosynthesis of amino acids, the building blocks of proteins. The fueling reactions of central metabolism provide precursor metabolites for synthesis of the 20 amino acids incorporated into proteins. Thus, synthesis of an amino acid entails a dual cost: energy is lost by diverting chemical intermediates from fueling reactions and additional energy is required to convert precursor metabolites to amino acids. Among amino acids, costs of synthesis vary from 12 to 74 high-energy phosphate bonds per molecule. The energetic advantage to encoding a less costly amino acid in a highly expressed gene can be greater than 0.025% of the total energy budget. Here, we provide evidence that amino acid composition in the proteomes of\n            <jats:italic>E. coli<\/jats:italic>\n            and\n            <jats:italic>Bacillus subtilis<\/jats:italic>\n            reflects the action of natural selection to enhance metabolic efficiency. We employ synonymous codon usage bias as a measure of translation rates and show increases in the abundance of less energetically costly amino acids in highly expressed proteins.\n          <\/jats:p>","DOI":"10.1073\/pnas.062526999","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:37:36Z","timestamp":1027694256000},"page":"3695-3700","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":626,"title":["Metabolic efficiency and amino acid composition in the proteomes of\n            <i>Escherichia coli<\/i>\n            and\n            <i>Bacillus subtilis<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"Hiroshi","family":"Akashi","sequence":"first","affiliation":[{"name":"Institute of Molecular Evolutionary Genetics and Department of Biology, 208 Mueller Laboratory, Pennsylvania State University, University Park, PA 16802; and Center for Information Biology, National Institute of Genetics, Mishima 411-8540, Japan"}]},{"given":"Takashi","family":"Gojobori","sequence":"additional","affiliation":[{"name":"Institute of Molecular Evolutionary Genetics and Department of Biology, 208 Mueller Laboratory, Pennsylvania State University, University Park, PA 16802; and Center for Information Biology, National Institute of Genetics, Mishima 411-8540, Japan"}]}],"member":"341","published-online":{"date-parts":[[2002,3,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/2251025a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.164.3881.788"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-516304-0.50006-4"},{"key":"e_1_3_3_4_2","first-page":"185","volume-title":"Molecular Evolution","author":"Li W-H","year":"1997","unstructured":"W-H Li Molecular Evolution (Sinauer, Sunderland, MA), pp. 185\u2013190 (1997)."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1961.026.01.009"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(97)00403-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1017028102013"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a026257"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.24.12165"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.15.3174"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.1997.0443"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a025981"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.6.1481"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/341245a0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061052"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0141-8130(99)00006-9"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.0942"},{"key":"e_1_3_3_18_2","first-page":"64","volume-title":"The Hypercycle, a Principle of Natural Self-Organization","author":"Eigen M","year":"1979","unstructured":"M Eigen, P Schuster The Hypercycle, a Principle of Natural Self-Organization (Springer, Berlin), pp. 64 (1979)."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(87)90241-5"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.13.2525"},{"key":"e_1_3_3_21_2","volume-title":"Biochemistry","author":"Zubay G","year":"1998","unstructured":"G Zubay Biochemistry (Brown, 4th Ed., Dubuque, IA, 1998).","edition":"4"},{"key":"e_1_3_3_22_2","volume-title":"The Microbial World","author":"Stanier R Y","year":"1986","unstructured":"R Y Stanier, J L Ingraham, M L Wheelis, P R Painter The Microbial World (Prentice Hall, 5th Ed., Englewood Cliffs, NJ, 1986).","edition":"5"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.1.29"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.123"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/36786"},{"key":"e_1_3_3_26_2","first-page":"431","volume":"13","author":"Biaudet V","year":"1997","unstructured":"V Biaudet, F Samson, P Bessieres Comput Appl Biosci 13, 431\u2013438 (1997).","journal-title":"Comput Appl Biosci"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5331.1453"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.57.4.862-952.1993"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.130000"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00225-5"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.7.1397"},{"key":"e_1_3_3_33_2","first-page":"213","volume-title":"Statistical Methods","author":"Snedecor G W","year":"1989","unstructured":"G W Snedecor, W G Cochran Statistical Methods (Iowa State Univ. Press, 8th Ed., Ames), pp. 213\u2013215 (1989).","edition":"8"},{"key":"e_1_3_3_34_2","volume-title":"Physiology of the Bacterial Cell: A Molecular Approach","author":"Neidhardt F C","year":"1990","unstructured":"F C Neidhardt, J L Ingraham, M Schaechter Physiology of the Bacterial Cell: A Molecular Approach (Sinauer, Sunderland, MA, 1990)."},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a025646"},{"key":"e_1_3_3_36_2","first-page":"213","volume":"12","author":"Kanaya S","year":"1996","unstructured":"S Kanaya, Y Kudo, Y Nakamura, T Ikemura Comput Appl Biosci 12, 213\u2013225 (1996).","journal-title":"Comput Appl Biosci"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1558-5646.1989.tb04220.x"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)02108-9"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02578899"},{"key":"e_1_3_3_40_2","first-page":"2067","volume-title":"Escherichia coli and Salmonella: Cellular and Molecular Biology","author":"VanBogelen R A","year":"1996","unstructured":"R A VanBogelen, K Z Abshire, A Pertsemlidis, R L Clark, F C Neidhardt Escherichia coli and Salmonella: Cellular and Molecular Biology, eds F C Neidhardt, R Curtis, J L Ingraham, E C C Lin, K B Low, B Magasanik, W S Reznikoff, M Riley, A Schaecter, H E Umbarger (Am. Soc. Microbiol., 2nd Ed., Washington, DC), pp. 2067\u20132117 (1996).","edition":"2"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.20.6425-6440.1999"},{"key":"e_1_3_3_42_2","first-page":"13","volume":"2","author":"Ikemura T","year":"1985","unstructured":"T Ikemura Mol Biol Evol 2, 13\u201334 (1985).","journal-title":"Mol Biol Evol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.54.2.198-210.1990"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-437X(94)90070-1"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.17.5025-5040.2001"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/85686"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.062526999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T19:08:02Z","timestamp":1649790482000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.062526999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,3,19]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2002,3,19]]}},"alternative-id":["10.1073\/pnas.062526999"],"URL":"https:\/\/doi.org\/10.1073\/pnas.062526999","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,3,19]]},"assertion":[{"value":"2001-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-03-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}