Journal of Molecular Evolution

, Volume 39, Issue 5, pp 519–527 | Cite as

Phylogenetic relationships among eutherian orders estimated from inferred sequences of mitochondrial proteins: Instability of a tree based on a single gene

  • Ying Cao
  • Jun Adachi
  • Axel Janke
  • Svante Pääbo
  • Masami Hasegawa


The phylogenetic relationships among Primates (human), Artiodactyla (cow), Cetacea (whale), Carnivora (seal), and Rodentia (mouse and rat) were estimated from the inferred amino acid sequences of the mitochondrial genomes using Marsupialia (opossum), Aves (chicken), and Amphibia (Xenopus) as an outgroup. The overall evidence of the maximum likelihood analysis suggests that Rodentia is an outgroup to the other four eutherian orders and that Cetacea and Artiodactyla form a clade with Carnivora as a sister taxon irrespective of the assumed model for amino acid substitutions. Although there remains an uncertainty concerning the relation among Artiodactyla, Cetacea, and Carnivora, the existence of a clade formed by these three orders and the outgroup status of Rodentia to the other eutherian orders seems to be firmly established. However, analyses of individual genes do not necessarily conform to this conclusion, and some of the genes reject the putatively correct tree with nearly 5% significance. Although this discrepancy can be due to convergent or parallel evolution in the specific genes, it was pointed out that, even without a particular reason, such a discrepancy can occur in 5% of the cases if the branching among the orders in question occurred within a short period. Due to uncertainty about the assumed model underlying the phylogenetic inference, this can occur even more frequently. This demonstrates the importance of analyzing enough sequences to avoid the danger of concluding an erroneous tree.

Key words

Opossum Outgroup Branching order Mammalian evolution Maximum likelihood tree 


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  1. Adachi J, Hasegawa M (1992a) Computer Science Monographs, No. 27. MOLPHY: Programs for Molecular Phylogenetics, I. —PROTML: Maximum Likelihood Inference of Protein Phylogeny. Institute of Statistical Mathematics, TokyoGoogle Scholar
  2. Adachi J, Hasegawa M (1992b) Amino acid substitution of proteins coded for in mitochondrial DNA during mammalian evolution. Jpn J Genet 67:187–197PubMedGoogle Scholar
  3. 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 36:270–281Google Scholar
  4. Akaike H (1974) A new look at the statistical model identification. IEEE Trans Autom Contr AC-19:716–723Google 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 290:457–464PubMedGoogle 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 156:683–717Google Scholar
  7. Árnason Ú, Gullberg A, Widegren B (1991) The complete nucleotide sequence of the mitochondrial DNA of the fin whale, Balaenoptera physalus. J Mol Evol 33:556–568Google Scholar
  8. Árnason Ú, Johnsson E (1992) The complete mitochondrial DNA sequence of the harbor seal, Phoca vitulina. J Mol Evol 34:493–505Google Scholar
  9. Bibb MJ, Van Etten RA, Wright CT, Walberg MW, Clayton DA (1981) Sequence and gene organization of mouse mitochondrial DNA. Cell 26:167–180Google Scholar
  10. Brown WM, Prager EM, Wang A, Wilson AC (1982) Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol 18:225–239Google Scholar
  11. Bulmer M, Wolfe KH, Sharp PM (1991) Synonymous nucleotide substitution rates in mammalian genes: implications for the molecular clock and the relationship of mammalian orders. Proc Natl Acad Sci U S A 88:5974–5978Google Scholar
  12. Czelusniak J, Goodman M, Koop BF, Tagle DA, Shoshani J, Braunitzer G, Kleinschmidt TK, de Jong WW, Matsuda G (1990) Perspectives from amino acid and nucleotide sequences on cladistic relationships among higher taxa of Eutheria. In: Genoways HH (ed) Current mammalogy, vol 2. Plenum Press, New York, pp 545–572Google Scholar
  13. 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
  14. Desjardins P, Morais R (1990) Sequence and gene organization of the chicken mitochondrial genome: a novel gene order in higher vertebrates. J Mol Biol 212:599–634PubMedGoogle Scholar
  15. Easteal S (1990) The pattern of mammalian evolution and the relative rate of molecular evolution. Genetics 124:165–173Google Scholar
  16. Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791Google Scholar
  17. Felsenstein J (1990) PHYLIP, Version 3.3. University Washington, SeattleGoogle Scholar
  18. Fukami-Kobayashi K, Tateno Y (1991) Robustness of maximum likelihood tree estimation against different patterns of base substitutions. J Mol Evol 32:79–91Google Scholar
  19. Gadaleta G, Pepe G, De Candia G, Quagliariello C, Sbisa E, Saccone C (1989) The complete nucleotide sequence of the Rattus norvegicus mitochondrial genome: cryptic signals revealed by comparative analysis between vertebrates. J Mol Evol 28:497–516Google Scholar
  20. Graur D (1993) Molecular phylogeny and the higher classification of eutherian mammals. Trends Ecol Evol 8:141–147Google Scholar
  21. Hasegawa M, Kishino H, Yano T (1985) Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol 22:160–174PubMedGoogle Scholar
  22. Hasegawa M, Cao Y, Adachi J, Yano T (1992) Rodent polyphyly? Nature 355:595–595Google Scholar
  23. Hasegawa M, Fujiwara M (1993) Relative efficiencies of the maximum likelihood, maximum parsimony, and neighbor-joining methods for estimating protein phylogeny. Mol Phyl Evol 2:1–5Google Scholar
  24. Hasegawa M, Hashimoto T, Adachi J, Iwabe N, Miyata T (1993) Early divergences in the evolution of eukaryotes: ancient divergence of Entamoeba that lacks mitochondria revealed by protein sequence data. J Mol Evol 36:380–388PubMedGoogle Scholar
  25. Hasegawa M (1994) Inference of evolutionary trees from DNA and protein sequence data. In: Bozdogan H (ed) The frontiers of statistical modeling: an informational approach, vol 3. Engineering and Scientific Applications, Kluwer Academic Publ, Dordrecht, pp 241–248Google Scholar
  26. Hasegawa M, Kishino H (1994) Accuracies of the simple methods for estimating the bootstrap probability of a maximum likelihood tree. Mol Biol Evol 11:142–145Google Scholar
  27. Hashimoto T, Otaka E, Adachi J, Mizuta K, Hasegawa M (1993) The giant panda is most close to a bear, judged by α- and β-hemoglobin sequences. J Mol Evol 36:282–289Google Scholar
  28. Hashimoto T, Nakamura Y, Nakamura F, Shirakura T, Adachi J, Goto N, Okamoto K, Hasegawa M (1994) Protein phylogeny gives a robust estimation for early divergences of eukaryotes: phylogenetic place of a mitochondria-lacking protozoan, Giardia lamblia. Mol Biol Evol 11:65–71Google Scholar
  29. 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 35:32–43Google Scholar
  30. Janke A, Feldmaier-Fuchs G, Thomas WK, von Haeseler A, Pääbo S (1994) The marsupial mitochondrial genome and the evolution of placental mammals. Genetics 137:243–256Google Scholar
  31. Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matrices from protein sequences. Comp Appl Biosci 8:275–282Google 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 29:170–179PubMedGoogle Scholar
  33. Kishino H, Miyata T, Hasegawa M (1990) Maximum likelihood inference of protein phylogeny and the origin of chloroplasts. J Mol Evol 30:151–160Google Scholar
  34. Kojima S, Hashimoto T, Hasegawa M, Murata S, Ohta S, Seki H, Okada N (1993) Close phylogenetic relationship between Vestimentifera (tube worms) and Annelida revealed by the amino acid sequence of elongation factor-1α. J Mol Evol 37:66–70Google Scholar
  35. Li W-H, Gouy M, Sharp PM, O'hUigin C, Yang Y-W (1990) Molecular phylogeny of Rodentia, Lagomorpha, Primates, Artiodactyla, and Carnivora and molecular clocks. Proc Natl Acad Sci USA 87:6703–6707Google Scholar
  36. McKenna MC (1975) Toward a phylogenetic classification of the mammalia. In: Luckett WP, Szalay FS (eds) Phylogeny of the primates: a multidisciplinary approach. Plenum Press, New York, pp 21–46Google Scholar
  37. Novacek MJ (1992) Mammalian phylogeny: shaking the tree. Nature 356:121–125Google Scholar
  38. Roe BA, Ma D-P, Wilson RK, Wong JF-H (1985) The complete nucleotide sequence of the Xenopus laevis mitochondrial genome. J Biol Chem 260:9759–9774Google Scholar
  39. Romer AS (1966) Vertebrate paleontology. University of Chicago Press, ChicagoGoogle Scholar
  40. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425PubMedGoogle Scholar
  41. Sakamoto Y, Ishiguro M, Kitagawa G (1986) Akaike information criterion statistics. D Reidel Publ Comp, DordrechtGoogle Scholar
  42. Simpson GG (1945) The principles of classification and a classification of mammals. Bull Am Mus Nat Hist 85:1–350Google Scholar
  43. Stewart C-B, Schilling JW, Wilson AC (1987) Adaptive evolution in the stomach lysozymes of foregut fermenters. Nature 330:401–404Google Scholar
  44. Wyss AR, Novacek MJ, McKenna MC (1987) Amino acid sequence versus morphological data and the interordinal relationships of mammals. Mol Biol Evol 4:99–116Google Scholar

Copyright information

© Springer-Verlag New York Inc 1994

Authors and Affiliations

  • Ying Cao
    • 1
  • Jun Adachi
    • 2
  • Axel Janke
    • 3
  • Svante Pääbo
    • 3
  • Masami Hasegawa
    • 1
    • 2
  1. 1.The Institute of Statistical MathematicsMinato-ku, TokyoJapan
  2. 2.Department of Statistical ScienceThe Graduate University for Advanced StudiesMinato-ku, TokyoJapan
  3. 3.Department of ZoologyUniversity of MunichMunich 2Germany

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