Summary
Based on the rates of synonymous substitution in 42 protein-codin gene pairs from rat and human, a correlation is shown to exist between the frequency of the nucleotides in all positions of the codon and the synonymous substitution rate. The correlation coefficients were positive for A and T and negative for C and G. This means that AT-rich genes accumulate more synonymous substitutions than GC-rich genes. Biased patterns of mutation could not account for this phenomenon. Thus, the variation in synonymous substitution rates and the resulting unequal codon usage must be the consequence of selection against A and T in synonymous positions. Most of the varition in rates of synonymous substitution can be explained by the nucleotide composition in synonymous positions. Codon-anticodon interactions, dinucleotide frequencies, and contextual factors influence neither the rates of synonymous substitution nor codon usage. Interestingly, the nucleotide in the second position of codons (always a nonsynonymous position) was found to affect the rate of synonymous substitution. This finding links the rate of nonsynonymous substitution with the synonymous rate. Consequently, highly conservative proteins are expected to be encoded by genes that evolve slowly in terms of synonymous substitutions, and are consequently highly biased in their codon usage.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Andersen RD, Birren BW, Ganz T, Piletz JE, Herschman HR (1983) Molecular cloning of the rat metallothionein 1 (mt-1) mRNA sequence. DNA 2:15–22
Andersen RD, Birren BW, Taplitz SJ, Herschman HR (1986) Rat metallothionein-1 structural gene and three pseudogenes, one of which contains 5′ regulatory sequences. Mol Cell Biol 6:302–314
Aota S, Ikemura T (1986) Diversity in G+C content at the third position of codons in vertebrate genes and its cause. Nucleic Acids Res 14:6345–6355 +Erratum 14:8702
Aota S, Gojobori T, Maruyama T, Ikemura T (1988) Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res 16:r315-r402
Argentin S, Nemer M, Drouin J, Scott GK, Kennedy BP, Davies PL (1985) The gene for rat atrial natriuretic factor. J Biol Chem 260:4568–4571
Argos P, Taylor WL, Minth CD, Dixon JE (1983) Nucleotide and amino acid sequence comparisons of preprosomatostatins. J Biol Chem 258:8788–8793
Ayer D, Yarus M (1986) The context effect does not require a fourth base pair. Science 231:393–395
Benfield PA, Zivin RA, Miller LS, Sowder R, Smythers GW, Henderson L, Oroszlan S, Pearson ML (1984) Isolation and sequence analysis of cDNA clones coding for rat skeletal muscle creatine kinase. J Biol Chem 259:14979–14984
Bennetzen JL, Hall BD (1982) Codon selection in yeast. J Biol Chem 257:3026–3031
Boguski MS, Elshourbagy NA, Taylor JM, Gordon JI (1985) Comparative analysis of repeated sequences in rat apolipoproteins A-I, A-IV and E. Proc Natl Acad Sci USA 82:992–996
Bulmer M (1987a) A statistical analysis of nucleotide sequences of introns and exons in human genes. Mol Biol Evol 4:395–405
Bulmer M (1987b) Coevolution of codon usage and transfer RNA abundance Nature 325:728–730
Bulmer M (1988) Are codon usage patterns in unicellular organisms determined by selection-mutation balance? J Evol Biol 1:15–26
Chang ACY, Cochet M, Cohen SN (1980) Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide. Proc Natl Acad Sci USA 77:4890–4894
Chang LMS (1973) Low molecular weight deoxyribonucleic acid polymerase from calf thymus chromatin. J Biol Chem 248:6983–6992
Chen KCK, Chen JS, Johnson JL (1986) Structural features of multiplemifH-like sequences and very biased codon usage in nitrogenase genes ofClostridium pasteurianum. J Bacteriol 166:162–172
Chin WW, Godine JE, Klein DR, Chang AS, Tan LK, Habener JF (1983) Nucleotide sequence of the cDNA encoding the precursor of the β subunit of rat leutropin. Proc Natl Acad Sci USA 80:4649–4653
Cooke NE, Baxter JD (1982) Structural analysis of the prolactin gene suggests a separate origin for its 5′ end. Nature 297:603–606
Cowan NJ, Dobner PR, Fuchs EV, Cleveland DW (1983) Expression of human α-tubulin genes: interspecies conservation of 3′ untranslated regions. Mol Cell Biol 3:1738–1745
Crabtree GR, Comeau CM, Fowlkes DM, Fornace AJ, Malley JD, Kant JA (1985) Evolution and structure of the fibrinogen genes: random insertion of introns or selective loss? J Mol Biol 185:1–19
den Dunnen JT, Moormann RJM, Lubsen NH, Schoenmakers JGG (1986) Intron insertions and deletions in the β/γ-crystallin gene family: the rat βB1 gene. Proc Natl Acad Sci USA 83:2855–2859
Deschenes RJ, Haun RS, Funckes CL, Dixon JE (1985) A gene encoding rat cholecystokinin: isolation, nucleotide sequence and promoter activity. J Biol Chem 260:1280–1286
Drouin J, Goodman HM (1980) Most of the coding region of rat ACTH-β-LPH precursor gene lacks intervening sequences. Nature 288:610–613
Dugaiczyk A, Law SW, Dennison OE (1982) Nucleotide sequence and the encoded amino acids of human serum albumin mRNA. Proc Natl Acad Sci USA 79:71–75
Dull TJ, Gray A, Hayflick JS, Ullrich A (1984) Insulin-like growth factor II precursor gene organization in relation to insulin gene family. Nature 310:777–781
Fiddes JC, Goodman HM (1981) The gene encoding the common α subunit of the four glycoprotein hormones. J Mol Appl Genet 1:3–18
Fort PH, Marty L, Piechaczyk M, el Sabrouty S, Dani C, Jeanteur P, Blanchard JM (1985) Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res 13:1431–1442
Ginzburg I, Behar L, Givol D, Littauer UZ (1981) The nucleotide sequence of rat α-tubulin: 3′-end characteristics, and evolutionary conservation. Nucleic Acids Res 9:2691–2697
Godine JE, Chin WW, Habener JF (1982) α subunit of rat pituitary glycoprotein hormones. J Biol Chem 257:8368–8371
Gojobori T, Li WH, Graur D (1982) Patterns of nucleotide substitution in pseudogenes and functional genes. J Mol Evol 18:360–369
Gouy M, Gautier C (1982) Codon usage in bacteria: correlation with gene expression. Nucleic Acids Res 10:7055–7074
Graeme IB, Merryweather JP, Sanchez-Pescador RP, Stempien MM, Priestley L, Scott J, Rall LB (1984) Sequence of a cDNA clone encoding human preproinsulin-like growth factor II. Nature 310:775–777
Graur D (1985) Amino acid composition and the evolutionary rates of protein-coding genes. J Mol Evol 22:53–62
Graur D, Shuali Y, Li WC (1988) Deletions in processed pseudogenes accumulate faster in rodents than in humans. J Mol Evol (in press)
Greenberg BD, Bencen GH, Seilhamer JJ, Lewicki JA, Fiddes JC (1984) Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor. Nature 312:656–658
Grosjena H, Fiers W (1982) Preferential codon usage in prokaryotic genes: the optimal codon-anticodon interaction energy and the selective codon usage in efficiently expressed genes. Gene 18:199–209
Grosjean H, Sankoff D, Min Jou W, Fiers W, Cedergren RJ (1978) BacteriophageMS2 RNA: a correlation between the stability of codon-anticodon interaction and the choice of codon words. J Mol Evol 12:113–119
Hall L, Craig RK, Edbrooke MR, Campbell PN (1982) Comparison of the nucleotide sequence of cloned human and guineapig pre-α lactalbumin cDNA with that of chick pre-lysozyme cDNA suggests evolution from a common ancestral gene. Nucleic Acids Res 10:3503–3515
Hamada H, Petrino MG, Kakunaga T (1982) Molecular structure and evolutionary origin of human cardiac muscle actin gene. Proc Natl Acad Sci USA 79:5901–5905
Hanauer A, Mandel JL (1984) The glyceraldehyde-3-phosphate dehydrogenase gene family: structure of a human cDNA and of an X chromosome linked pseudogene; amazing complexity of the gene family in the mouse. EMBO J 3:2627–2633
Hastings KEM, Emerson CP (1983) Codon usage in muscle genes and liver genes. J Mol Evol 19:214–218
Hatfield D, Rice M (1986) Aminoacyl-tRNA (anticodon): codon adaptation in human and rabbit reticulocytes. Biochem Int 13:835–842
Hayashizaki Y, Miyai K, Kato K, Matsubara K (1985) Molecular cloning of human thyrotropin-β subunit gene. FEBS Lett 188:394–400
Heinrich G, Kronenberg HM, Potts JT, Habener JF (1984) Gene encoding parathyroid hormone: nucleotide sequence of the rat gene deduced amino acid sequence of rat preproparathyroid hormone. J Biol Chem 259:3320–3329
Hudson P, Haley J, Cronk M, Shine J, Niall H (1981) Molecular cloning and characterization of cDNA sequences coding for rat relaxin. Nature 291:127–131
Hudson P, John M, Crawford R, Haralambidis J, Scanlon D, Gorman J, Tregear G, Shine J, Niall H (1984) Relaxin gene expression in human ovaries and thepredicted struture of human preprorelaxin by analysis of cDNA clones. EMBO J 3:2333–2339
Ikemura T (1980) The frequency of codon usage inE. coli genes: correlation with the abundance of cognate tRNA. In: Osawa S, Ozeki H, Uchida H, Yura T (eds) Genetics and evolution of RNA polymerase, tRNA and ribosomes. University of Tokyo Press, Tokyo, pp 519–523
Ikemura T (1981a) Correlation between the abundance ofEscherichia coli transfer RNAs and the occurrence of the repetitive codon in protein genes. J Mol Biol 146:1–21
Ikemura T (1981b) Correlation between the abundance ofEscherichia coli transfer RNAs and the occurrence of the repetitive codon in protein genes: a proposal for a synonymous codon choice that is optimal for theE. coli translational system. J Mol Biol 151:389–409
Ikemura T (1982) Correlation between the abundance of yeast transfer RNAs and the occurrence of the repetitive codon in protein genes: differences in synonymous codon choice patterns of yeast andEscherichia coli with references to the abundance of isoacceptor transfer RNAs. J Mol Biol 158:573–579
Ikemura T (1985) Codon usage and tRNA content in unicellular and multicellular organisms. Mol Biol Evol 2:13–34
Ikemura T, Ozeki H (1983) Codon usage and transfer RNA contents: organism-specific codon choice patterns in reference to isoacceptor contents. Cold Spring Harbor Symp Quant Biol 42:1087–1097
Inana G, Totsuka S, Redmond M, Dougherty T, Nagle J, Shiono T, Ohura T, Kominami E, Katunuma N (1986) Molecular cloning of human ornithine aminotransferase mRNA. Proc Natl Acad Sci USA 83:1203–1207
Jagodzinski LL, Sargent TD, Yang M, Glackin C, Bonner J (1981) Sequence homology between RNAs encoding rat α-fetoprotein and rat serum albumin. Proc Natl Acad Sci USA 78: 3521–3525
Joh K, Mukai T, Yatsuki H, Hori K (1985) Rat aldolase-A messenger RNA: the nucleotide sequence and multiple mRNA species with different 5′-terminal regions. Gene 39:17–24
Jukes TH, King JL (1979) Evolutionary nucleotide replacements in DNA. Nature 281:605–606
Karathanasis SK (1985) Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes. Proc Natl Acad Sci USA 82:6374–6378
Karin M, Richards RI (1982) Human metallothionein gene —primary structure of the metallothionein-II gene and a related processed gene. Nature 299:797–802
Kawakami K, Nojima H, Ohta T, Nagano K (1986) Molecular cloning and sequence analysis of human Na+, K+-ATPase β-subunit. Nucleic Acids Res 14:2833–2844
Kimura M (1977) Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature 267:275–276
Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, Cambridge
Law SW, Brewer HB (1984) Nucleotide sequence and the encoded amino acids of human apolipoprotein A-I mRNA. Proc Natl Acad Sci USA 81:66–70
Leibold EA, Munro HN (1987) Characterization and evolution of the expressed rat ferritin light subunit gene and its pseudogene family. J Biol Chem 262:7335–7341
Li SSL, Fitch WM, Pan YCE, Sharief FS (1983) Evolutionary relationship of vertebrate lactate dehydrogenase isozymes A4 (muscle), B4 (heart), and C4 (testis). J Biol Chem 258:7029–7032
Li WH, Tanimura M (1987) The molecular clock runs more slowly in man than in apes and monkeys. Nature 326:93–96
Li WH, Wu CI (1987) Rates of nucleotide substitution are evidently higher in rodents than in man. Mol Biol Evol 4: 74–77
Li WH, Gojobori T, Nei M (1981) Pseudogenes as a paradigm of neutral evolution. Nature 292:237–239
Li WH, Wu CI, Luo CC (1984) Nonrandomness of point mutation as reflected in nucleotide substitutions and its evolutionary implications. J Mol Evol 21:58–71
Li WH, Luo CC, Wu CI (1985a) Evolution of DNA sequences. In: MacIntyre RJ (ed) Molecular evolutionary genetics. Plenum, New York, pp 1–94
Li WH, Wu CI, Luo CC (1985b) A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2:150–174
Li WH, Tanimura M, Sharp PM (1987) An evaluation of the molecular clock hypothesis using mammalian DNA sequences. J Mol Evol 25:330–342
Lipman DJ, Wilbur WJ (1983) Contexual constraints on synonymous codon choice. J Mol Biol 163:363–376
Loeb LA, Kunkel TA (1982) Fidelity of DNA synthesis. Annu Rev Biochem 52:429–457
Lopez LC, Farzier ML, Su CJ, Kumar A, Saunders GF (1983) Mammalian pancreatic preproglucagon contains three glucagon-related peptides. Proc Natl Acad Sci USA 80:5484–5489
Luo CC, Li WH, Moore MN, Chan L (1986) Structure and evolution of the apolipoprotein multigene family. J Mol Biol 187:325–340
MacDonald RJ, Crerar MM, Swain WF, Pictet RL, Thomas G, Rutter WJ (1980) Structure of a family of rat amylase genes. Nature 287:117–122
Mayer Y, Czosnek H, Zeelon PE, Yaffe D, Nudel U (1984) Expression of the genes coding for the skeletal muscle and cardiac actins in the heart. Nucleic Acids Res 12:1087–1100
McLean JW, Fukazawa C, Taylor JM (1983) Rat apolipoprotein E mRNA: cloning and sequencing of double-stranded cDNA. J Biol Chem 258:8993–9000
McLean JW, Elshourbagy NA, Chang DJ, Mahley RW, Taylor JM (1984) Human apolipoprotein E mRNA: cDNA cloning and nucleotide sequence of a new variant. J Biol Chem 259: 6498–6504
Meakin SO, Breitman ML, Tsui LC (1985) Structural and evolutionary relationships among five members of the human γ-crystallin gene family. Mol Cell Biol 5:1408–1414
Miyata T, Hayashida H (1981) Extraordinarily high evolutionary rate of pseudogenes: evidence for the presence of selective pressure against changes between synonymous codons. Proc Natl Acad Sci USA 78:5739–5743
Miyata T, Yasunaga T (1981) Rapidly evolving mouse α-globin-related pseudogene and its evolutionary history. Proc Natl Acad Sci USA 78:450–453
Miyata T, Yasunaga T, Nishida T (1980) Nucleotide sequence divergence and functional constraint in mRNA evolution. Proc Natl Acad Sci USA 77:7328–7332
Modrich P (1987) DNA mismatch correction. Annu Rev Biochem 56:435–466
Morinaga T, Sakai M, Wegmann TG, Tamaoki T (1983) Primary structures of human α-fetoprotein and its mRNA. Proc Natl Acad Sci USA 80:4604–4608
Moriuchi T, Chang HC, Denome R, Rilver J (1982)Thy-1 cDNA sequence suggests a novel regulatory mechanism. Nature 301:80–82
Mouchiroud D (1986) Relation entre la composition en base de l'ADN non codant du gene et la composition en codon. CR Acad Sci Paris 303:743–748
Mueckler MM, Pitot HC (1985) Sequence of the precursor to the rat ornithine aminotransferase deduced from a cDNA clone. J Biol Chem 250:12993–12997
Nakamura Y, Ogawa M, Nishide T, Emi M, Kosaki G, Himeno S, Matsubara K (1984) Sequences of cDNAs for human salivary and pancreatic α-amylases. Gene 28:263–270
Newgard CB, Nakano K, Hwang PK, Fletterick RJ (1986) Sequence analysis of the complementary DNA encoding human liver glycogen phosphorylase reveals tissue-specific codon usage. Proc Natl Acad Sci USA 83:8132–8136
Ng SY, Gunning P, Eddy R, Ponte P, Leavitt J, Shows T, Kedes L (1985) Evolution of the functional human β-actin gene and its multipseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol 5:2720–2732
Nichols BP, Miozzari GF, van Cleemput M, Bennett GM, Yanofsky C (1980) Nucleotide sequences of thetrpG regions ofEscherichia coli, Shigella dysenteriae, Salmonella typhimurium andSerratia marcescens. J Mol Biol 142:503
Nie NH, Hadlaihull C, Jenkins JG, Steinbrenner K, Bent DH (1975) SPSS. McGraw-Hill, New York
Nudel U, Zakut R, Shani M, Neuman S, Levy Z, Yaffe D (1983) The nucleotide sequence of the rat cytoplasmic β-actin gene. Nucleic Acids Res 11:1759–1771
Nussinov R (1981) Eukaryotic dinucleotide preference rules and their implications for degenerate codon usage. J Mol Biol 149:125–131
Osawa S, Chiu RH, McDonough A, Miller TB, Johnson GL (1986) Isolation of partial cDNAs for rat liver and muscle glycogen phosphorylase isozymes. FEBS Lett 202:282–288
Ouenzar B, Agoutin B, Reinisch F, Weill D, Perin F, Keith G, Heyman T (1988) Distribution of isoaccepting tRNAs and codons for proline and glycine in collagenous and noncollagenous chicken tissues. Biochem Biophys Res Commun 150: 148–155
Page GS, Smith S, Goodman GM (1981) DNA sequence of the rat growth hormone gene: location of the 5′ terminus of the growth hormone mRNA and identification of an internal transposon-like element. Nucleic Acids Res 9:2087–2104
Perryman MB, Kerner SA, Bohlmeyer TJ, Roberts R (1986) Isolation and sequence analysis of a full-length cDNA for human M creatine kinase. Biochem Biophys Res Commun 140:981–989
Precup J, Parker J (1987) Missense misreading of asparagine codons as a function of codon identity and context. J Biol Chem 262:11351–11355
Qasba PK, Safaya SK (1984) Similarity of the nucleotide sequences of rat α-lactalbumin and chicken lysozyme gene. Nature 303:377–380
Rixon MW, Chan WY, Davie EW, Chung DW (1983) Characterization of a complementary deoxyribonucleic acid coding for the α-chain of human fibrinogen. Biochemistry 22: 3237–3244
Rosenberger RF, Hilton J (1983) The frequency of transcriptional and translational errors at nonsense codons in thelacZ gene ofEscherichia coli. Mol Gen Genet 191:207–212
Roskam WG, Rougeon F (1979) Molecular cloning and nucleotide sequence of the human growth hormone structural gene. Nucleic Acids Res 7:305–320
Rottmann WH, Tolan DR, Penhoet EE (1984) Complete amino acid sequence for human aldolase B derived from cDNA and genomic clones. Proc Natl Acad Sci USA 81:2738–2742
Sakakibara M, Mukai T, Hori K (1985) Nucleotide sequence of a cDNA clone for human aldolase: a messenger RNA in the liver. Biochem Biophys Res Commun 131:413–420
Santoro C, Marone M, Ferrone M, Costanzo F, Colombo M, Minganti C, Cortese R, Silengo L (1986) Cloning of the gene coding for human L apoferritin. Nucleic Acids Res 14:721–735
Sargent TD, Yang M, Booner J (1981) Nucleotide sequence of cloned rat serum albumin messenger RNA. Proc Natl Acad Sci USA 78:243–246
Sausville E, Carney D, Battey J (1985) The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line. J Biol Chem 260:10236–10241
Sharp PM, Li WH (1987a) The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. Mol Biol Evol 4:222–230
Sharp PM, Li WH (1987b) The codon adaptation index—a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res 15:1281–1294
Shen LP, Pictet RL, Rutter WJ (1982) Human somatostatin sequence of the cDNA. Proc Natl Acad Sci USA 79:4575–4579
Shpaer EG (1986) Constraint on codon context inEscherichia coli genes. Their possible role in modulating the efficiency of translation. J Mol Biol 188:555–564
Soares MB, Schon E, Henderson A, Karathanasis SK, Cate R, Zeitlin S, Chirgwin J, Efstratiadis A (1985) RNA-mediated duplication: the rat preproinsulin I gene is a functional retroposon. Mol Cell Biol 5:2090–2103
Sueoka N (1988) Directional mutation pressure and neutral molecular evolution. Proc Natl Acad Sci USA 85:2653–2657
Sullivan KF, Havercroft JC, Cleveland DW (1984) Primary structure and expression of a vertebrate β-tubulin gene family. In: Dorisy GG, Cleveland DW, Murphy DW (eds) Molecular biology of the cytoskeleton. Cold Spring Harbor Press. Cold Spring Harbor NY, pp 321–332
Sundelin J, Melhus H, Das S, Eriksson U, Lind P, Traegardh L, Peterson PA, Rask L (1985) The primary structure of rabbit and rat prealbumin and a comparison with the tertiary structure of human prealbumin. J Biol Chem 260:6481–6487
Tajimi F, Nei M (1982) Biases of the estimates of DNA divergence obtained by the restriction enzyme technique. J Mol Evol 18:115–120
Takahashi Y, Kato K, Hayashizaki Y, Wakabayash T, Ohtsuka E, Matsuki S, Ikehara M, Matsubara K (1985) Molecular cloning of the human cholecystokinin gene by use of synthetic probe containing deoxyinosine. Proc Natl Acad Sci USA 82: 1931–1935
Truong AT, Duez C, Belayew A, Renard A, Pictet R, Bell GI, Martial JA (1984) Isolation and characterization of human prolactin gene. EMBO J 3:429–437
Tsujibo H, Tiano HF, Li SSL (1985) Nucleotide sequence of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A isozyme Eur J Biochem 147:9–15
Tsutsumi KI, Mukai T, Hidaka S, Miyahara H, Tsutsumi R, Tanaka T, Hori K, Ishikawa K (1983) Rat aldolase isozyme gene: cloning and characterization of cDNA for aldolase B messenger RNA. J Biol Chem 258:6537–6542
Ullrich A, Dull TJ, Gray A, Brosius J, Sures I (1980) Genetic variation in the human insulin gene. Science 209:612–615
van Rijs J, Giruere V, Hurst J, van Agthoven T, van Kessel AD, Goyert S, Grosveld F (1985) Chromosomal localization of humanthy-1 gene. Proc Natl Acad Sci USA 82:5832–5835
Varenne S, Buc J, Lloubes R, Lazdunski C (1984) Translation in a nonuniform process: effect of tRNA availability on the rate of elongation of nascent polypeptide chains. J Mol Biol 180:549–576
Varshney U, Gedamu L (1984) Human metallothionein MT-I and MT-II processed genes. Gene 31:135–145
Vasicek TJ, McCevitt BE, Freeman MW, Fennick BJ, Hendy GN, Potts JT, Rich A, Kronenberg HM (1983) Nucleotide sequence of the human parathyroid hormone gene. Proc Natl Acad Sci USA 80:2127–2131
Wain-Hobson S, Nussinov R, Brown RJ, Sussman JL (1981) Preferential codon usage in genes. Gene 13:335–364
Wallace MR, Naylor SL, Kluve-Beckerman, B, Long GL, McDonald L, Shows TB, Benson MD (1985) Localization of the human prealbumin gene to chromosome 18. Biochem Biophys Res Commun 129:753–758
Wells D, Bauis W, Kedes L (1986) Codon usage in histone gene families of higher eukaryotes reflects functional rather than phylogenetic relationships. J Mol Evol 23:224–241
White JW, Saunders GF (1986) Structure of the human glucagon gene. Nucleic Acids Res 14:4719–4730
Wilbur WJ, Lipman DJ (1985) Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci USA 80:726–730
Wilde CD, Crowther CE, Cripe TP, Gwo-Shu Lee M, Cowan NJ (1982) Evidence that a human β-tubulin pseudogene is derived from its corresponding mRNA. Nature 297:83–84
Wright S (1969) Evolution and genetics of populations, vol 2. University of Chicago Press, Chicago
Wu CI, Li WH (1985) Evidence for higher rates in rodents than in man. Proc Natl Acad Sci USA 82:1741–1745
Yanofsky C, van Cleemput M (1982) Nucleotide sequence of trpE ofSalmonella typhimurium and its homology with the corresponding sequence ofEscherichia coli. J Mol Biol 155: 235–246
Young RM, Shull GE, Lingrel JB (1987) Multiple mRNAs from rat kidney and brain encode a single Na+, K+-ATPase β-subunit protein. J Biol Chem 262:4905–4910
Zuckerkandl E (1965) Remarques sur l'évolution des polynucléotides comparée à celle des polypeptides. Bull Soc Chim Biol 47:1729–1730
Zuckerkandl E, Pauling L (1965) Molecules as documents of evolutionary history. J Theor Biol 8:357–366
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ticher, A., Graur, D. Nucleic acid composition, codon usage, and the rate of synonymous substitution in protein-coding genes. J Mol Evol 28, 286–298 (1989). https://doi.org/10.1007/BF02103424
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02103424