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.


Journal article



Publication Date





1429 - 1437


Africa South of the Sahara, Computer Simulation, Disease Outbreaks, Europe, Genes, env, Genes, gag, Genetic Variation, Genetics, Population, HIV Infections, HIV-1, Humans, Likelihood Functions, Logistic Models, Models, Genetic, Pedigree, Phylogeny, Predictive Value of Tests, Statistical Distributions