The causes and consequences of HIV evolution.
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AIDS Vaccines↗
Biomedical subjects
David Posada
Publications and source records attributed to David Posada.
Model selection and model averaging in phylogenetics: advantages of akaike information criterion and bayesian approaches over likelihood ratio tests.
Model selection is a topic of special relevance in molecular phylogenetics that affects many, if not all, stages of phylogenetic inference. Here we discuss some fundamental concepts and techniques of model selection in the context of phylogenetics. We start by reviewing different aspects of the selection of substitution models in phylogenetics from a theoretical, philosophical and practical point of view, and summarize this comparison in table format. We argue that the most commonly implemented model selection approach, the hierarchical likelihood ratio test, is not the optimal strategy for model selection in phylogenetics, and that approaches like the Akaike Information Criterion (AIC) and Bayesian methods offer important advantages. In particular, the latter two methods are able to simultaneously compare multiple nested or nonnested models, assess model selection uncertainty, and allow for the estimation of phylogenies and model parameters using all available models (model-averaged inference or multimodel inference). We also describe how the relative importance of the different parameters included in substitution models can be depicted. To illustrate some of these points, we have applied AIC-based model averaging to 37 mitochondrial DNA sequences from the subgenus Ohomopterus(genus Carabus) ground beetles described by Sota and Vogler (2001).
Animals↗
Evidence for survival of Pleistocene climatic changes in Northern refugia by the land snail Trochoidea geyeri (Soós 1926) (Helicellinae, Stylommatophora).
BACKGROUND: The study of organisms with restricted dispersal abilities and presence in the fossil record is particularly adequate to understand the impact of climate changes on the distribution and genetic structure of species. Trochoidea geyeri (Soós 1926) is a land snail restricted to a patchy, insular distribution in Germany and France. Fossil evidence suggests that current populations of T. geyeri are relicts of a much more widespread distribution during more favourable climatic periods in the Pleistocene. RESULTS: Phylogeographic analysis of the mitochondrial 16S rDNA and nuclear ITS-1 sequence variation was used to infer the history of the remnant populations of T. geyeri. Nested clade analysis for both loci suggested that the origin of the species is in the Provence from where it expanded its range first to Southwest France and subsequently from there to Germany. Estimated divergence times predating the last glacial maximum between 25-17 ka implied that the colonization of the northern part of the current species range occurred during the Pleistocene. CONCLUSION: We conclude that T. geyeri could quite successfully persist in cryptic refugia during major climatic changes in the past, despite of a restricted capacity of individuals to actively avoid unfavourable conditions.
Animals↗
Simulating haplotype blocks in the human genome.
SUMMARY: A bioinformatic tool was written to simulate haplotypes and SNPs under a modified coalescent with recombination. The most important feature of this program is that it allows for the specification of non-homogeneous recombination rates, which results in the formation of the so-called 'haplotype blocks' of the human genome. The program also implements different mutation models and flexible demographic histories. The samples generated can be very useful to better understand the architecture of the human genome and to investigate its impact in association studies searching for disease genes. AVAILABILITY: The SNPsim package is available at http://www.evolgenics.com/software
Algorithms↗
A coalescent model of recombination hotspots.
Recent experimental findings suggest that the assumption of a homogeneous recombination rate along the human genome is too naive. These findings point to block-structured recombination rates; certain regions (called hotspots) are more prone than other regions to recombination. In this report a coalescent model incorporating hotspot or block-structured recombination is developed and investigated analytically as well as by simulation. Our main results can be summarized as follows: (1) The expected number of recombination events is much lower in a model with pure hotspot recombination than in a model with pure homogeneous recombination, (2) hotspots give rise to large variation in recombination rates along the genome as well as in the number of historical recombination events, and (3) the size of a (nonrecombining) block in the hotspot model is likely to be overestimated grossly when estimated from SNP data. The results are discussed with reference to the current debate about block-structured recombination and, in addition, the results are compared to genome-wide variation in recombination rates. A number of new analytical results about the model are derived.
Computer Simulation↗
Recombination in evolutionary genomics.
Recombination can be a dominant force in shaping genomes and associated phenotypes. To better understand the impact of recombination on genomic evolution, we need to be able to identify recombination in aligned sequences. We review bioinformatic approaches for detecting recombination and measuring recombination rates. We also examine the impact of recombination on the reconstruction of evolutionary histories and the estimation of population genetic parameters. Finally, we review the role of recombination in the evolutionary history of bacteria, viruses, and human mitochondria. We conclude by highlighting a number of areas for future development of tools to help quantify the role of recombination in genomic evolution.
Base Sequence↗
The effect of recombination on the accuracy of phylogeny estimation.
Phylogenetic studies based on DNA sequences typically ignore the potential occurrence of recombination, which may produce different alignment regions with different evolutionary histories. Traditional phylogenetic methods assume that a single history underlies the data. If recombination is present, can we expect the inferred phylogeny to represent any of the underlying evolutionary histories? We examined this question by applying traditional phylogenetic reconstruction methods to simulated recombinant sequence alignments. The effect of recombination on phylogeny estimation depended on the relatedness of the sequences involved in the recombinational event and on the extent of the different regions with different phylogenetic histories. Given the topologies examined here, when the recombinational event was ancient, or when recombination occurred between closely related taxa, one of the two phylogenies underlying the data was generally inferred. In this scenario, the evolutionary history corresponding to the majority of the positions in the alignment was generally recovered. Very different results were obtained when recombination occurred recently among divergent taxa. In this case, when the recombinational breakpoint divided the alignment in two regions of similar length, a phylogeny that was different from any of the true phylogenies underlying the data was inferred.
Computer Simulation↗
Evaluation of methods for detecting recombination from DNA sequences: empirical data.
The performance of 14 different recombination detection methods was evaluated by analyzing several empirical data sets where the presence of recombination has been suggested or where recombination is assumed to be absent. In general, recombination methods seem to be more powerful with increasing levels of divergence, but different methods showed distinct performance. Substitution methods using summary statistics gave more accurate inferences than most phylogenetic methods. However, definitive conclusions about the presence of recombination should not be derived on the basis of a single method. Performance patterns observed from the analysis of real data sets coincided very well with previous computer simulation results. Previous recombination inferences from some of the data sets analyzed here should be reconsidered. In particular, recombination in HIV-1 seems to be much more widespread than previously thought. This finding might have serious implications on vaccine development and on the reliability of previous inferences of HIV-1 evolutionary history and dynamics.
DNA↗
Phylogeographic history of the land snail Candidula unifasciata (Helicellinae, Stylommatophora): fragmentation, corridor migration, and secondary contact.
We studied sequence variation in 16S rDNA in 204 individuals from 37 populations of the land snail Candidula unifasciata (Poiret 1801) across the core species range in France, Switzerland, and Germany. Phylogeographic, nested clade, and coalescence analyses were used to elucidate the species evolutionary history. The study revealed the presence of two major evolutionary lineages that evolved in separate refuges in southeast France as result of previous fragmentation during the Pleistocene. Applying a recent extension of the nested clade analysis (Templeton 2001), we inferred that range expansions along river valleys in independent corridors to the north led eventually to a secondary contact zone of the major clades around the Geneva Basin. There is evidence supporting the idea that the formation of the secondary contact zone and the colonization of Germany might be postglacial events. The phylogeographic history inferred for C. unifasciata differs from general biogeographic patterns of postglacial colonization previously identified for other taxa, and it might represent a common model for species with restricted dispersal.
Animals↗