Abstract
The hepatitis B virus (HBV) has a circular DNA genome of about 3,200 base pairs. Economical use of the genome with overlapping reading frames may have led to severe constraints on nucleotide substitutions along the genome and to highly variable rates of substitution among nucleotide sites. Nucleotide sequences from 13 complete HBV genomes were compared to examine such variability of substitution rates among sites and to examine the phylogenetic relationships among the HBV variants. The maximum likelihood method was employed to fit models of DNA sequence evolution that can account for the complexity of the pattern of nucleotide substitution. Comparison of the models suggests that the rates of substitution are different in different genes and codon positions; for example, the third codon position changes at a rate over ten times higher than the second position. Furthermore, substantial variation of substitution rates was detected even after the effects of genes and codon positions were corrected; that is, rates are different at different sites of the same gene or at the same codon position. Such rates after the correction were also found to be positively correlated at adjacent sites, which indicated the existence of conserved and variable domains in the proteins encoded by the viral genome. A multiparameter model validates the earlier finding that the variation in nucleotide conservation is not random around the HBV genome. The test for the existence of a molecular clock suggests that substitution rates are more or less constant among lineages. The phylogenetic relationships among the viral variants were examined. Although the data do not seem to contain sufficient information to resolve the details of the phylogeny, it appears quite certain that the serotypes of the viral variants do not reflect their genetic relatedness.
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Bichko V, Pushko P, Dreilina P, Pumpen P, Gren E (1985) Subtype ayw variant of hepatitis B virus: DNA primary structure analysis. FEBS Lett 185:208–212
Estacio RC, Chavez CC, Okamoto H, Lingao AL, Reyes MT, Domingo E, Mayumi M (1988) Nucleotide sequence of a hepatitis B virus genome of subtype adw isolated from a Philippino: comparison with the reported three genomes of the same subtype. J Gastroenterol Hepatol 3:215–222
Felsenstein J (1981) Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol 17:368–376
Felsenstein J (1993) PHYLIP: phylogenetic inference package, version 3.5. University of Washington, Seattle
Fujiyama A, Miyanohara A, Nozaki C, Yoneyama T, Ohtomo N, Matsubara K (1983) Cloning and structural analysis of hepatitis B virus DNAs subtype adr. Nucleic Acids Res 11:4601–4610
Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P (1979) Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 281:646–650
Gan R, Chu M, Shen L, Li ZF (1987) The complete nucleotide sequence of the cloned DNA of hepatitis B virus subtype adr in pADR-1. Sci China [B] 30:507–521
Gill PE, Murray W, Wright MH (1981) Practical optimization. Academic Press, London
Goldman N (1993a) Statistical tests of models of DNA substitution. J Mot Evol 36:182–198
Goldman N (1993b) Simple diagnostic statistical tests of models for DNA substitution. J Mot Evol 37:650–661
Goldman N, Yang Z (1994) A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11: 725–736
Grimmett GR, Stirzaker DR (1992) Probability and random processes, 2nd ed. Clarendon Press, Oxford, pp 239–246
Hasegawa M, Kishino H (1989) Confidence limits on the maximum likelihood estimation of the hominoid tree from mitochondrial DNA sequences. Evolution 43:672–677
Iswari R, Okamoto H, Mayumi M, Warsa UC, Sujudi (1985) The complete nucleotide sequence of an HBV DNA clone subtype adw (pRTB299) from Indonesia. ICMR Ann 5:39–50
Jin L, Nei M (1990) Limitations of the evolutionary parsimony method of phylogenetic analysis. Mol Biol Evol 7:82–102
Kendall MG, Stuart A (1973) The advanced theory of statistics, vol 2, 3rd ed. Charles Griffin & Company, London, pp 234–237
Kishino H, Hasegawa M (1989) Evaluation of maximum likelihood estimate of the evolutionary tree topologies from DNA sequence data, and the branching order in Hominoidea. J Mol Evol 29:170–179
Kobayashi M, Koike K (1984) Complete nucleotide sequence of hepatitis B virus DNA of subtype adr and its conserved gene organization. Gene 30:227–232
Lauder IJ, Lin HJ, Lau JYN, Sin TS, Lai CL (1993) The variability of the hepatitis B virus genome: statistical analysis and biological implications. Mol Biol Evol 10: 457–470
Li W-H (1993) Unbiased estimation of the rates of synonymous and nonsynonymous substitution. Mol Biol Evol 36:96–99
Li W-H, Wu C-I, Luo C-C (1985) A new method for estimating synonymous and nonsynonymous rates of nucleotide substitutions considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2:150–174
Lin HJ (1989) Biochemical detection of hepatitis B virus constituents. Adv Clin Chem 27:143–199
Miyata T, Yasunaga T (1980) Molecular evolution of mRNA: a method for estimating evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences and its application. J Mol Evol 16:23–36
Muse SV, Gaut BS (1994) A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to chloroplast genome. Mol Biol Evol 11:715–724
Nei M, Gojobori T (1986) Simple methods for estimating the number of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426
Okamoto H, Imai H, Kametani M, Nakamura T, Mayumi M (1987) Genomic heterogeneity of hepatitis B virus in a 54-year-old woman who contracted the infection through materno-fetal transmission. Jpn J Exp Med 57:231–236
Okamoto H, Imai M, Shimozaki M, Hochi Y, Iizuka H, Gotanda T, Tsuda F, Miyakawa Y, Mayumi M (1986) Nucleotide sequence of a cloned hepatitis B virus genome subtype adr: comparison with genomes of other three subtypes. J Gen Virol 67:2305–2314
Ono Y, Onda H, Sasada R, Igarishi K, Sugino Y, Nishioka K (1983) The complete nucleotide sequence of the cloned hepatitis B virus subtype adr and adw. Nucleic Acids Res 11:1747–1757
Orito E, Mizokami M, Ina Y, Moriyama EN, Kameshima N, Yamamoto M, Gojobori T (1989) Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proc Natl Acad Sci USA 86:7059–7062
Pamilo P, Bianchi NO (1993) Evolution of the Zfx and Zfy genes—rates and interdependence between the genes. Mol Biol Evol 10:271–281
Pugh JC, Weber C, Houston H, Murray K (1986) Expression of the X gene of hepatitis B virus. J Med Virol 30:229–246
Rho MR, Kim K, Hyun SW, Kim YS (1989) The nucleotide sequence and reading frames of a mutant hepatitis B virus subtype adr. Nucleic Acids Res 17:2124
Tamura K, Nei M (1993) Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol 10:512–526
Tateno Y, Takezaki N, Nei M (1994) Relative efficiencies of the maximum-likelihood, neighbor-joining, and maximum-parsimony methods when substitution rate varies with site. Mol Biol Evol 11:261–277
Valenzuela P, Quiroga M, Zaldivar J, Gray P, Rutter WJ (1981) The nucleotide sequence of the hepatitis B viral genome and the identification of the major viral genes. In: Fields B, Jalnisch R, Fox CF (eds) Animal virus genetics. Academic Press, New York, pp 57–70
Wakeley J (1993) Substitution rate variation among sites in hypervariable region 1 of human mitochondrial DNA. J Mol Evol 37:613–623
Yang Z (1993) Maximum likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites. Mol Biol Evol 10:1396–1401
Yang Z (1994a) Estimating the pattern of nucleotide substitution. J Mol Evol 39:105–111
Yang Z (1994b) Maximum likelihood phylogenetic estimation from DNA sequences with variable rates over sites: approximate methods. J Mol Evol 39:306–314
Yang Z, Wang T (in press) Mixed model analysis of DNA sequence evolution. Biometrics
Yang Z, Goldman N, Friday AE (1994) Comparison of models for nucleotide substitution used in maximum likelihood phylogenetic estimation. Mol Biol Evol 11:316–324
Yang Z, Goldman N, Friday AE (1995) Maximum likelihood trees from DNA sequences: a peculiar statistical estimation problem. Syst Biol 44:385–400
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Correspondence to: Z. Yang
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Yang, Z., Lauder, I.J. & Lin, H.J. Molecular evolution of the hepatitis B virus genome. J Mol Evol 41, 587–596 (1995). https://doi.org/10.1007/BF00175817
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DOI: https://doi.org/10.1007/BF00175817