Journal of Molecular Evolution

, Volume 33, Issue 2, pp 114–124 | Cite as

An evolutionary model for maximum likelihood alignment of DNA sequences

  • Jeffrey L. Thorne
  • Hirohisa Kishino
  • Joseph Felsenstein


Most algorithms for the alignment of biological sequences are not derived from an evolutionary model. Consequently, these alignment algorithms lack a strong statistical basis. A maximum likelihood method for the alignment of two DNA sequences is presented. This method is based upon a statistical model of DNA sequence evolution for which we have obtained explicit transition probabilities. The evolutionary model can also be used as the basis of procedures that estimate the evolutionary parameters relevant to a pair of unaligned DNA sequences. A parameter-estimation approach which takes into account all possible alignments between two sequences is introduced; the danger of estimating evolutionary parameters from a single alignment is discussed.

Key words

DNA sequence alignment Maximum likelihood procedure Dynamic programming Evolutionary model Insertion-deletion model 


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  1. Allison L, Yee CN (1990) Minimum message length and the comparison of macromoecules. Bull Math Biol 52:431–453Google Scholar
  2. Bishop MJ, Thompson EA (1986) Maximum likelihood alignment of DNA sequences. J Mol Biol 190:159–165Google Scholar
  3. Feller W (1968) An introduction to probability theory and its applications, vol I, 3rd ed. McGraw-Hill, New York, pp 480–481Google Scholar
  4. Felsenstein J (1981a) A likelihood approach to character weighting and what it tells us about parsimony and compatibility. Biol J Linn Soc 16:183–196Google Scholar
  5. Felsenstein J (1981b) Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol 17:368–376Google Scholar
  6. Fitch WM, Smith TF (1983) Optimal sequence alignments. Proc Natl Acad Sci USA 80:1382–1386Google Scholar
  7. Gotoh O (1982) An improved algorithms for matching biological sequences. J Mol Biol 162:705–708Google Scholar
  8. Hasegawa M, Kishino H, Yano T (1985) Dating of the humanape spliting by a molecular clock of mitochondrial DNA. J Mol Evol 22:160–174Google Scholar
  9. Hein J (1990) A unified approach to alignment and phylogenies. In: Doolittle RF (ed) Methods in enzymology, vol 183. Academic Press, San Diego, pp 626–645Google Scholar
  10. Jukes TH, Cantor CR (1969) Evolution of protein molecules. In: Munro HN (ed) Mammalian protein metabolism. Academic Press, New York, pp 21–132Google Scholar
  11. Kendall M, Stuart A (1973) The advanced theory of statistics, vol 2, ed 3. Charles Griffen, London, pp 45–46Google Scholar
  12. Kimura M (1980) A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16:111–120Google Scholar
  13. Needleman SB, Wunsch CD (1970) A general method applicable to the search for similarities in the amino acid sequences of two proteins. J Mol Biol 48:444–453Google Scholar
  14. Nelder JA, Mead R (1965) A simplex method for function minimization. Comput J 7:308–313Google Scholar
  15. Press WH, Flannery BP, Teukolsky SA, Vetterling WT (1988) Numerical recipes in C. Cambridge University Press, New York, pp 305–309Google Scholar
  16. Reichert TA, Cohen DN, Wong AKC (1973) An application of information theory to genetic mutations and the matching of polypeptide sequences. J Theor Biol 42:245–261Google Scholar
  17. Sankoff D, Kruskal JB (eds) (1983) Time warps, string edits, and macromolecules: the theory and practice of sequence comparison. Addison-Wesley, Reading MAGoogle Scholar
  18. Schaaper RM, Danforth BN, Glickman BW (1986) Mechanisms of spontaneous mutagenesis: an analysis of the spectrum of spontaneous mutation inEscherichia coli lacI gene. J Mol Biol 189:273–284Google Scholar
  19. Waterman MS (1983) Sequence alignments in the neighborhood of the optimum with general application to dynamic programming. Proc Natl Acad Sci USA 80:3123–3124Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1991

Authors and Affiliations

  • Jeffrey L. Thorne
    • 1
  • Hirohisa Kishino
    • 1
  • Joseph Felsenstein
    • 1
  1. 1.Department of Genetics SK-50University of WashingtonSeattleUSA

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