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. 2000 Jul;155(3):1429–1437. doi: 10.1093/genetics/155.3.1429

An integrated framework for the inference of viral population history from reconstructed genealogies.

O G Pybus 1, A Rambaut 1, P H Harvey 1
PMCID: PMC1461136  PMID: 10880500

Abstract

We describe a unified set of methods for the inference of demographic history using genealogies reconstructed from gene sequence data. We introduce the skyline plot, a graphical, nonparametric estimate of demographic history. We discuss both maximum-likelihood parameter estimation and demographic hypothesis testing. Simulations are carried out to investigate the statistical properties of maximum-likelihood estimates of demographic parameters. The simulations reveal that (i) the performance of exponential growth model estimates is determined by a simple function of the true parameter values and (ii) under some conditions, estimates from reconstructed trees perform as well as estimates from perfect trees. We apply our methods to HIV-1 sequence data and find strong evidence that subtypes A and B have different demographic histories. We also provide the first (albeit tentative) genetic evidence for a recent decrease in the growth rate of subtype B.

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Selected References

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  1. Di Rienzo A., Wilson A. C. Branching pattern in the evolutionary tree for human mitochondrial DNA. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1597–1601. doi: 10.1073/pnas.88.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Donnelly P., Tavaré S. Coalescents and genealogical structure under neutrality. Annu Rev Genet. 1995;29:401–421. doi: 10.1146/annurev.ge.29.120195.002153. [DOI] [PubMed] [Google Scholar]
  3. Felsenstein J. Estimating effective population size from samples of sequences: inefficiency of pairwise and segregating sites as compared to phylogenetic estimates. Genet Res. 1992 Apr;59(2):139–147. doi: 10.1017/s0016672300030354. [DOI] [PubMed] [Google Scholar]
  4. Fu Y. X. A phylogenetic estimator of effective population size or mutation rate. Genetics. 1994 Feb;136(2):685–692. doi: 10.1093/genetics/136.2.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grassly N. C., Harvey P. H., Holmes E. C. Population dynamics of HIV-1 inferred from gene sequences. Genetics. 1999 Feb;151(2):427–438. doi: 10.1093/genetics/151.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Griffiths R. C., Tavaré S. Sampling theory for neutral alleles in a varying environment. Philos Trans R Soc Lond B Biol Sci. 1994 Jun 29;344(1310):403–410. doi: 10.1098/rstb.1994.0079. [DOI] [PubMed] [Google Scholar]
  7. 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. doi: 10.1007/BF02101694. [DOI] [PubMed] [Google Scholar]
  8. Kuhner M. K., Yamato J., Felsenstein J. Estimating effective population size and mutation rate from sequence data using Metropolis-Hastings sampling. Genetics. 1995 Aug;140(4):1421–1430. doi: 10.1093/genetics/140.4.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kuhner M. K., Yamato J., Felsenstein J. Maximum likelihood estimation of population growth rates based on the coalescent. Genetics. 1998 May;149(1):429–434. doi: 10.1093/genetics/149.1.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leitner T., Albert J. The molecular clock of HIV-1 unveiled through analysis of a known transmission history. Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10752–10757. doi: 10.1073/pnas.96.19.10752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Leitner T., Kumar S., Albert J. Tempo and mode of nucleotide substitutions in gag and env gene fragments in human immunodeficiency virus type 1 populations with a known transmission history. J Virol. 1997 Jun;71(6):4761–4770. doi: 10.1128/jvi.71.6.4761-4770.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Li W. H., Tanimura M., Sharp P. M. Rates and dates of divergence between AIDS virus nucleotide sequences. Mol Biol Evol. 1988 Jul;5(4):313–330. doi: 10.1093/oxfordjournals.molbev.a040503. [DOI] [PubMed] [Google Scholar]
  13. Nee S., Holmes E. C., Rambaut A., Harvey P. H. Inferring population history from molecular phylogenies. Philos Trans R Soc Lond B Biol Sci. 1995 Jul 29;349(1327):25–31. doi: 10.1098/rstb.1995.0087. [DOI] [PubMed] [Google Scholar]
  14. Polanski A., Kimmel M., Chakraborty R. Application of a time-dependent coalescence process for inferring the history of population size changes from DNA sequence data. Proc Natl Acad Sci U S A. 1998 May 12;95(10):5456–5461. doi: 10.1073/pnas.95.10.5456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pybus O. G., Holmes E. C., Harvey P. H. The mid-depth method and HIV-1: a practical approach for testing hypotheses of viral epidemic history. Mol Biol Evol. 1999 Jul;16(7):953–959. doi: 10.1093/oxfordjournals.molbev.a026184. [DOI] [PubMed] [Google Scholar]
  16. Rambaut A., Grassly N. C. Seq-Gen: an application for the Monte Carlo simulation of DNA sequence evolution along phylogenetic trees. Comput Appl Biosci. 1997 Jun;13(3):235–238. doi: 10.1093/bioinformatics/13.3.235. [DOI] [PubMed] [Google Scholar]
  17. Rayfield M. A., Downing R. G., Baggs J., Hu D. J., Pieniazek D., Luo C. C., Biryahwaho B., Otten R. A., Sempala S. D., Dondero T. J. A molecular epidemiologic survey of HIV in Uganda. HIV Variant Working Group. AIDS. 1998 Mar 26;12(5):521–527. doi: 10.1097/00002030-199805000-00014. [DOI] [PubMed] [Google Scholar]
  18. Robbins K. E., Kostrikis L. G., Brown T. M., Anzala O., Shin S., Plummer F. A., Kalish M. L. Genetic analysis of human immunodeficiency virus type 1 strains in Kenya: a comparison using phylogenetic analysis and a combinatorial melting assay. AIDS Res Hum Retroviruses. 1999 Mar 1;15(4):329–335. doi: 10.1089/088922299311295. [DOI] [PubMed] [Google Scholar]
  19. Robertson J. R., Bucknall A. B., Welsby P. D., Roberts J. J., Inglis J. M., Peutherer J. F., Brettle R. P. Epidemic of AIDS related virus (HTLV-III/LAV) infection among intravenous drug abusers. Br Med J (Clin Res Ed) 1986 Feb 22;292(6519):527–529. doi: 10.1136/bmj.292.6519.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Slatkin M., Hudson R. R. Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations. Genetics. 1991 Oct;129(2):555–562. doi: 10.1093/genetics/129.2.555. [DOI] [PMC free article] [PubMed] [Google Scholar]

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