Journal of Molecular Evolution

, Volume 42, Issue 4, pp 459–468 | Cite as

Model of amino acid substitution in proteins encoded by mitochondrial DNA

  • Jun Adachi
  • Masami Hasegawa


Mitochondrial DNA (mtDNA) sequences are widely used for inferring the phylogenetic relationships among species. Clearly, the assumed model of nucleotide or amino acid substitution used should be as realistic as possible. Dependence among neighboring nucleotides in a codon complicates modeling of nucleotide substitutions in protein-encoding genes. It seems preferable to model amino acid substitution rather than nucleotide substitution. Therefore, we present a transition probability matrix of the general reversible Markov model of amino acid substitution for mtDNA-encoded proteins. The matrix is estimated by the maximum likelihood (ML) method from the complete sequence data of mtDNA from 20 vertebrate species. This matrix represents the substitution pattern of the mtDNA-encoded proteins and shows some differences from the matrix estimated from the nuclear-encoded proteins. The use of this matrix would be recommended in inferring trees from mtDNA-encoded protein sequences by the ML method.

Key words

General reversible Markov model Amino acid substitution Maximum likelihood method 


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  1. Adachi J (1995) Modeling of molecular evolution and maximum likelihood inference of molecular phylogeny. PhD dissertation, The Graduate University for Advanced Studies, Tokyo, JapanGoogle Scholar
  2. Adachi J, Cao Y, Hasegawa M (1993) Tempo and mode of mitochondrial DNA evolution in vertebrates at the amino acid sequence level: rapid evolution in warm-blooded vertebrates. J Mol Evol 36:270–281PubMedCrossRefGoogle Scholar
  3. Adachi J, Hasegawa M (1995) Phylogeny of whales: dependence of the inference on species sampling. Mol Biol Evol 12:177–179PubMedGoogle Scholar
  4. Adachi J, Hasegawa M (1996) MOLPHY: programs for molecular phylogenetics, ver 2.3. Institute of Statistical Mathematics, TokyoGoogle Scholar
  5. Anderson S, Bankier AT, Barrell BG, de Bruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith ALH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–464PubMedCrossRefGoogle Scholar
  6. Anderson S, de Bruijn MHL, Coulson AR, Eperon IC, Sanger F, Young IG (1982) The complete sequence of bovine mitochondrial DNA: conserved features of the mammalian mitochondrial genome. J Mol Biol 156:683–717PubMedCrossRefGoogle Scholar
  7. Árnason Ú, Gullberg A (1993) Comparison between the complete mtDNA sequences of the blue and the fin whale, two species that can hybridize in nature. J Mol Evol 37:312–322PubMedGoogle Scholar
  8. Árnason Ú, Gullberg A, Johnsson E, Ledje C (1993) The nucleotide sequence of the mitochondrial DNA molecule of the grey seal,Halichoerus grypus, and a comparison with mitochondrial sequences of other true seals. J Mol Evol 37:323–330PubMedGoogle Scholar
  9. Árnason Ú, Gullberg A, Widegren B (1991) The complete nucleotide sequence of the mitochondrial DNA of the fin whale,Balaenoptera physalus. J Mol Evol 33:556–568PubMedCrossRefGoogle Scholar
  10. Árnason Ú, Johnsson E (1992) The complete mitochondrial DNA sequence of the harbor seal,Phoca vitulina. J Mol Evol 34:493–505PubMedCrossRefGoogle Scholar
  11. Bibb MJ, Van Etten RA, Wright CT, Walberg MW, Clayton DA (1981) Sequence and gene organization of mouse mitochondrial DNA. Cell 26:167–180PubMedCrossRefGoogle Scholar
  12. Brown WM, Prager EM, Wang A, Wilson AC (1982) Mitochondrial DNA sequences of primtes: tempo and mode of evolution. J Mol Evol 18:225–239PubMedCrossRefGoogle Scholar
  13. Cao Y, Adachi J, Janke A, Pääbo S, Hasegawa M (1994) Phylogenetic relationships among eutherian orders estimated from inferred sequences of mitochondrial proteins: instability of a tree based on a single gene. J Mol Evol 39:519–527PubMedCrossRefGoogle Scholar
  14. Chang YS, Huang FL, Lo TB (1994) The complete nucleotide sequence and gene organization of carp (Cyprinus carpio) mitochondrial genome. J Mol Evol 38:138–155PubMedCrossRefGoogle Scholar
  15. Collins TM, Wimberger PH, Naylor GJP (1994) Compositional bias, character-state bias, and character-state reconstruction using parsimony. Syst Biol 43:482–496CrossRefGoogle Scholar
  16. Dayhoff MO, Schwartz RM, Orcutt BC (1978) A model of evolutionary change in proteins. In: Dayhoff MO (ed) Atlas of protein sequence and structure, vol 5, suppl 3. National Biomedical Research Foundation, Washington DC, pp 345–352Google Scholar
  17. Desjardins P, Morais R (1990) Sequence and gene organization of the chicken mitochondrial genome: a novel gene order in higher vertebrates. J Mol Biol 212:599–634PubMedCrossRefGoogle Scholar
  18. Edwards AWF (1995) Assessing molecular phylogenies. Science 267:253–253PubMedGoogle Scholar
  19. Felsenstein J (1981) Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol 17:368–376PubMedCrossRefGoogle Scholar
  20. Gadaleta G, Pepe G, De Candia G, Quagliariello C, Sbisa E, Saccone C (1989) The complete nucleotide sequence of theRattus norvegicus mitochondrial genome: cryptic signals revealed by comparative analysis between vertebrates. J Mol Evol 28:497–516PubMedGoogle Scholar
  21. Goldman N (1990) Maximum likelihood inference of phylogenetic trees, with special reference to a Poisson process model of DNA substitution and to parsimony analyses. Syst Zool 39:345–361CrossRefGoogle Scholar
  22. Goldman N, Yang Z (1994) A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11:725–736PubMedGoogle Scholar
  23. Grantham R (1974) Amino acid differences formula to help explain protein evolution. Science 185:862–864PubMedCrossRefGoogle Scholar
  24. Hasegawa M, Fujiwara M (1993) Relative efficiencies of the maximum likelihood, maximum parsimony, and neighbor-joining methods for estimating protein phylogeny. Mol Phyl Evol 2:1–5CrossRefGoogle Scholar
  25. Hasegawa M, Kishino H (1989) Heterogeneity of tempo and mode of mitochondrial DNA evolution among mammalian orders. Jpn J Genet 64:243–258PubMedGoogle Scholar
  26. Horai S, Hayasaka K, Kondo R, Tsugane K, Takahata N (1995) The recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs. Proc Natl Acad Sci USA 92:532–536PubMedCrossRefGoogle Scholar
  27. Horai S, Satta Y, Hayasaka K, Kondo R, Inoue T, Ishida T, Hayashi S, Takahata N (1992) Man's place in Hominoidea revealed by mitochondrial DNA genealogy. J Mol Evol 35:32–43PubMedCrossRefGoogle Scholar
  28. Irwin DM, Kocher TD, Wilson AC (1991) Evolution of the cytochromeb gene of mammals. J Mol Evol 32:128–144PubMedGoogle Scholar
  29. Janke A, Feldmaier-Fuchs G, Thomas WK, von Haeseler A, Pääbo S (1994) The marsupial mitochondrial genome and the evolution of placental mammals. Genetics 137:243–256PubMedGoogle Scholar
  30. Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matrices from protein sequences. Comp Appl Biosci 8:275–282PubMedGoogle Scholar
  31. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  32. Kishino H, Hasegawa M (1989) Evaluation of the maximum likelihood estimate of the evolutionary tree topologies from DNA sequence data, and the branching order in Hominoidea. J Mol Evol 29:170–179PubMedCrossRefGoogle Scholar
  33. Kishino H, Miyata T, Hasegawa M (1990) Maximum likelihood inference of protein phylogeny, and the origin of chloroplasts. J Mol Evol 31:151–160CrossRefGoogle Scholar
  34. Lee WJ, Kocher TD (1995) Complete sequence of a sea lamprey (Petromyzon marinus) mitochondrial genome: early establishment of the vertebrate genome organization. Genetics 139:873–887PubMedGoogle Scholar
  35. McLachlan AD (1971) Tests for comparing related amino-acid sequences. Cytochromec and cytochromec 551. J Mol Biol 61:409–424PubMedCrossRefGoogle Scholar
  36. Muse SV, Gaut BS (1994) A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome. Mol Biol Evol 11:715–724PubMedGoogle Scholar
  37. Naylor GJP, Collins TM, Brown WM (1995) Hydrophobicity and phylogeny. Nature 373:565–566PubMedCrossRefGoogle Scholar
  38. Ozawa T, Tanaka M, Ino H, Ohno K, Sano T, Wada Y, Yoneda M, Tanno Y, Miyatake T, Tanaka T, Itoyama S, Ikebe S, Hattori N, Mizuno Y (1991) Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomy-opathies and Parkinson's disease. Biochem Biophys Res Commun 176:938PubMedCrossRefGoogle Scholar
  39. Perna NT, Kocher TD (1995) Unequal base frequencies and the estimation of substitution rates. Mol Biol Evol 12:359–361Google Scholar
  40. Roe BA, Ma DP, Wilson RK, Wong JFH (1985) The complete nucleotide sequence of theXenopus laevis mitochondrial genome. J Biol Chem 260:9759–9774PubMedGoogle Scholar
  41. Schöniger M, Hofacker GL, Borstnik B (1990) Stochastic traits of molecular evolution—acceptance of point mutations in native actin genes. J Theor Biol 143:287–306PubMedGoogle Scholar
  42. Sidow A (1994) Parsimony of statistics? Nature 367:26–26PubMedCrossRefGoogle Scholar
  43. Stewart CB (1993) The powers and pitfalls of parsimony. Nature 361:603–607PubMedCrossRefGoogle Scholar
  44. Tanaka M, Ozawa T (1994) Strand asymmetry in human mitochondrial DNA mutations. Genomics 22:327–335PubMedCrossRefGoogle Scholar
  45. Thorne JL, Kishino H, Felsenstein J (1992) Inching toward reality: an improved likelihood model of sequence evolution. J Mol Evol 34:3–16PubMedCrossRefGoogle Scholar
  46. Tzeng CS, Hui CF, Shen Huang PC (1992) The complete nucleotide sequence of theCrossostoma lacustre mitochondrial genome: conservation and variations among vertebrates. Nucleic Acids Res 20:4853–4858PubMedGoogle Scholar
  47. Xu X, Árnason Ú (1994) The complete mitochondrial DNA sequence of the horse,Equus caballus: extensive heteroplasmy of the control region. Gene 148:357–362PubMedCrossRefGoogle Scholar
  48. Yang Z (1994) Estimating the pattern of nucleotide substitution. J Mol Evol 39:105–111PubMedGoogle Scholar
  49. Zardoya R, Garrido-Pertierra A, Bautista JM (1995) The complete nucleotide sequence of mitochondrial DNA genome of the rainbow trout,Oncorhynchus mykiss. J Mol Evol 41:942–951PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1996

Authors and Affiliations

  • Jun Adachi
    • 1
  • Masami Hasegawa
    • 2
  1. 1.Department of Statistical ScienceThe Graduate University for Advanced StudiesTokyoJapan
  2. 2.The Institute of Statistical MathematicsTokyoJapan

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