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J Virol. Jun 1997; 71(6): 4761–4770.
PMCID: PMC191698

Tempo and mode of nucleotide substitutions in gag and env gene fragments in human immunodeficiency virus type 1 populations with a known transmission history.

Abstract

The complex evolutionary process of human immunodeficiency virus type 1 (HIV-1) is marked by a high level of genetic variation. It has been shown that the HIV-1 genome is characterized by variable and more constant regions, unequal nucleotide frequencies, and preference for G-to-A substitutions. However, this knowledge has largely been neglected in phylogenetic analyses of HIV-1 nucleotide sequences, even though these analyses are applied to a number of important biological questions. The purpose of this study was to identify a realistic model of HIV-1 evolution and to statistically test if the application of such a model significantly improves the accuracy of phylogenetic analyses. A unique and recently reported HIV-1 transmission cluster consisting of nine infected individuals, for whom the direction and time for each transmission were exactly known, formed the basis for the analyses which were performed under a general model of nucleotide substitution using population sequences from the env V3 and p17gag regions of the HIV-1 genome. Examination of seven different substitution models by maximum-likelihood methods revealed that the fit of the general reversible (REV) model was significantly better than that of simpler models, indicating that it is important to account for the asymmetric substitution pattern of HIV-1 and that the nucleotide substitution rate varied significantly across sites. The shape parameter alpha, which describes the variation across sites by a gamma distribution, was estimated to be 0.38 and 0.25 for env V3 and p17gag, respectively. In env V3, the estimated average transition/transversion rate ratio was 1.42. Thus, the REV model with variable rates across sites (described by a gamma distribution) provides the best description of HIV-1 evolution, whereas simple models are unrealistic and inaccurate. It is likely that the accuracy of phylogenetic studies of HIV-1 and many other viruses would improve substantially by the use of more realistic nucleotide substitution models. This is especially true when attempts are made to estimate the age of distant viral ancestors from contemporary viral sequences.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Albert J, Wahlberg J, Leitner T, Escanilla D, Uhlén M. Analysis of a rape case by direct sequencing of the human immunodeficiency virus type 1 pol and gag genes. J Virol. 1994 Sep;68(9):5918–5924. [PMC free article] [PubMed]
  • Baltimore D. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature. 1970 Jun 27;226(5252):1209–1211. [PubMed]
  • Berkhout B, van Hemert FJ. The unusual nucleotide content of the HIV RNA genome results in a biased amino acid composition of HIV proteins. Nucleic Acids Res. 1994 May 11;22(9):1705–1711. [PMC free article] [PubMed]
  • Bernardi G, Olofsson B, Filipski J, Zerial M, Salinas J, Cuny G, Meunier-Rotival M, Rodier F. The mosaic genome of warm-blooded vertebrates. Science. 1985 May 24;228(4702):953–958. [PubMed]
  • Coffin JM. Genetic diversity and evolution of retroviruses. Curr Top Microbiol Immunol. 1992;176:143–164. [PubMed]
  • Felsenstein J. Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol. 1981;17(6):368–376. [PubMed]
  • Gojobori T, Yamaguchi Y, Ikeo K, Mizokami M. Evolution of pathogenic viruses with special reference to the rates of synonymous and nonsynonymous substitutions. Jpn J Genet. 1994 Oct;69(5):481–488. [PubMed]
  • Hasegawa M, Kishino H, Yano T. Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol. 1985;22(2):160–174. [PubMed]
  • Hillis DM, Huelsenbeck JP, Cunningham CW. Application and accuracy of molecular phylogenies. Science. 1994 Apr 29;264(5159):671–677. [PubMed]
  • Holland JJ, De La Torre JC, Steinhauer DA. RNA virus populations as quasispecies. Curr Top Microbiol Immunol. 1992;176:1–20. [PubMed]
  • Hu WS, Temin HM. Retroviral recombination and reverse transcription. Science. 1990 Nov 30;250(4985):1227–1233. [PubMed]
  • Ikemura T, Aota S. Global variation in G+C content along vertebrate genome DNA. Possible correlation with chromosome band structures. J Mol Biol. 1988 Sep 5;203(1):1–13. [PubMed]
  • Katz RA, Skalka AM. Generation of diversity in retroviruses. Annu Rev Genet. 1990;24:409–445. [PubMed]
  • Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980 Dec;16(2):111–120. [PubMed]
  • Korber BT, Allen EE, Farmer AD, Myers GL. Heterogeneity of HIV-1 and HIV-2. AIDS. 1995;9 (Suppl A):S5–18. [PubMed]
  • Kumar S. Patterns of nucleotide substitution in mitochondrial protein coding genes of vertebrates. Genetics. 1996 May;143(1):537–548. [PMC free article] [PubMed]
  • Brown AL, Monaghan P. Evolution of the structural proteins of human immunodeficiency virus: selective constraints on nucleotide substitution. AIDS Res Hum Retroviruses. 1988 Dec;4(6):399–407. [PubMed]
  • Leitner T, Escanilla D, Franzén C, Uhlén M, Albert J. Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10864–10869. [PMC free article] [PubMed]
  • Leitner T, Escanilla D, Marquina S, Wahlberg J, Broström C, Hansson HB, Uhlén M, Albert J. Biological and molecular characterization of subtype D, G, and A/D recombinant HIV-1 transmissions in Sweden. Virology. 1995 May 10;209(1):136–146. [PubMed]
  • Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyö EM, Uhlén M. Analysis of heterogeneous viral populations by direct DNA sequencing. Biotechniques. 1993 Jul;15(1):120–127. [PubMed]
  • Leonard CK, Spellman MW, Riddle L, Harris RJ, Thomas JN, Gregory TJ. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990 Jun 25;265(18):10373–10382. [PubMed]
  • Li WH, Tanimura M, Sharp PM. Rates and dates of divergence between AIDS virus nucleotide sequences. Mol Biol Evol. 1988 Jul;5(4):313–330. [PubMed]
  • Louwagie J, McCutchan FE, Peeters M, Brennan TP, Sanders-Buell E, Eddy GA, van der Groen G, Fransen K, Gershy-Damet GM, Deleys R, et al. Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes. AIDS. 1993 Jun;7(6):769–780. [PubMed]
  • Mansky LM, Temin HM. Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J Virol. 1995 Aug;69(8):5087–5094. [PMC free article] [PubMed]
  • Moriyama EN, Ina Y, Ikeo K, Shimizu N, Gojobori T. Mutation pattern of human immunodeficiency virus gene. J Mol Evol. 1991 May;32(5):360–363. [PubMed]
  • Myers G, MacInnes K, Korber B. The emergence of simian/human immunodeficiency viruses. AIDS Res Hum Retroviruses. 1992 Mar;8(3):373–386. [PubMed]
  • Robertson DL, Sharp PM, McCutchan FE, Hahn BH. Recombination in HIV-1. Nature. 1995 Mar 9;374(6518):124–126. [PubMed]
  • Scarlatti G, Leitner T, Halapi E, Wahlberg J, Marchisio P, Clerici-Schoeller MA, Wigzell H, Fenyö EM, Albert J, Uhlén M, et al. Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1721–1725. [PMC free article] [PubMed]
  • Shpaer EG, Mullins JI. Rates of amino acid change in the envelope protein correlate with pathogenicity of primate lentiviruses. J Mol Evol. 1993 Jul;37(1):57–65. [PubMed]
  • Starcich BR, Hahn BH, Shaw GM, McNeely PD, Modrow S, Wolf H, Parks ES, Parks WP, Josephs SF, Gallo RC, et al. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. [PubMed]
  • Strunnikova N, Ray SC, Livingston RA, Rubalcaba E, Viscidi RP. Convergent evolution within the V3 loop domain of human immunodeficiency virus type 1 in association with disease progression. J Virol. 1995 Dec;69(12):7548–7558. [PMC free article] [PubMed]
  • SUEOKA N, MARMUR J, DOTY P., 2nd Dependence of the density of deoxyribonucleic acids on guanine-cytosine content. Nature. 1959 May 23;183(4673):1429–1431. [PubMed]
  • Sullivan J, Holsinger KE, Simon C. Among-site rate variation and phylogenetic analysis of 12S rRNA in sigmodontine rodents. Mol Biol Evol. 1995 Nov;12(6):988–1001. [PubMed]
  • Tamura K, Nei M. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol. 1993 May;10(3):512–526. [PubMed]
  • Temin HM. Retrovirus variation and reverse transcription: abnormal strand transfers result in retrovirus genetic variation. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6900–6903. [PMC free article] [PubMed]
  • Temin HM, Mizutani S. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature. 1970 Jun 27;226(5252):1211–1213. [PubMed]
  • Vartanian JP, Meyerhans A, Sala M, Wain-Hobson S. G-->A hypermutation of the human immunodeficiency virus type 1 genome: evidence for dCTP pool imbalance during reverse transcription. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3092–3096. [PMC free article] [PubMed]
  • Vartanian JP, Meyerhans A, Asjö B, Wain-Hobson S. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes. J Virol. 1991 Apr;65(4):1779–1788. [PMC free article] [PubMed]
  • Wakeley J. Substitution-rate variation among sites and the estimation of transition bias. Mol Biol Evol. 1994 May;11(3):436–442. [PubMed]
  • Yang Z. Estimating the pattern of nucleotide substitution. J Mol Evol. 1994 Jul;39(1):105–111. [PubMed]
  • Yang Z, Kumar S. Approximate methods for estimating the pattern of nucleotide substitution and the variation of substitution rates among sites. Mol Biol Evol. 1996 May;13(5):650–659. [PubMed]
  • Yokoyama S, Chung L, Gojobori T. Molecular evolution of the human immunodeficiency and related viruses. Mol Biol Evol. 1988 May;5(3):237–251. [PubMed]

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