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Biomedical subjects

A Rambaut

Publications and source records attributed to A Rambaut.

At least 19 recordsLinked to original sources
PubMed2003

The epidemiology and iatrogenic transmission of hepatitis C virus in Egypt: a Bayesian coalescent approach.

Hepatitis C virus (HCV) is a leading cause of liver cancer and cirrhosis, and Egypt has possibly the highest HCV prevalence worldwide. In this article we use a newly developed Bayesian inference framework to estimate the transmission dynamics of HCV in Egypt from sampled viral gene sequences, and to predict the public health impact of the virus. Our results indicate that the effective number of HCV infections in Egypt underwent rapid exponential growth between 1930 and 1955. The timing and speed of this spread provides quantitative genetic evidence that the Egyptian HCV epidemic was initiated and propagated by extensive antischistosomiasis injection campaigns. Although our results show that HCV transmission has since decreased, we conclude that HCV is likely to remain prevalent in Egypt for several decades. Our combined population genetic and epidemiological analysis provides detailed estimates of historical changes in Egyptian HCV prevalence. Because our results are consistent with a demographic scenario specified a priori, they also provide an objective test of inference methods based on the coalescent process.

Bayes Theorem↗
PubMed2002

New inferences from tree shape: numbers of missing taxa and population growth rates.

The relative positions of branching events in a phylogeny contain information about evolutionary and population dynamic processes. We provide new summary statistics of branching event times and describe how these statistics can be used to infer rates of species diversification from interspecies trees or rates of population growth from intraspecies trees. We also introduce a phylogenetic method for estimating the level of taxon sampling in a clade. Different evolutionary models and different sampling regimes can produce similar patterns of branching events, so it is important to consider explicitly the model assumptions involved when making evolutionary inferences. Results of an analysis of the phylogeny of the mosquito-borne flaviviruses suggest that there could be several thousand currently unidentified viruses in this clade.

Animals↗
PubMed2002

GENIE: estimating demographic history from molecular phylogenies.

UNLABELLED: GENIE implements a statistical framework for inferring the demographic history of a population from phylogenies that have been reconstructed from sampled DNA sequences. The methods are based on population genetic models known collectively as coalescent theory. AVAILABILITY: GENIE is available from http://evolve.zoo.ox.ac.uk. All popular operating systems are supported.

Computer Simulation↗
PubMed2001

The epidemic behavior of the hepatitis C virus.

Hepatitis C virus (HCV) is a leading worldwide cause of liver disease. Here, we use a new model of HCV spread to investigate the epidemic behavior of the virus and to estimate its basic reproductive number from gene sequence data. We find significant differences in epidemic behavior among HCV subtypes and suggest that these differences are largely the result of subtype-specific transmission patterns. Our model builds a bridge between the disciplines of population genetics and mathematical epidemiology by using pathogen gene sequences to infer the population dynamic history of an infectious disease.

Endemic Diseases↗
PubMed2001

Complete mitochondrial genome sequences of two extinct moas clarify ratite evolution.

The origin of the ratites, large flightless birds from the Southern Hemisphere, along with their flighted sister taxa, the South American tinamous, is central to understanding the role of plate tectonics in the distributions of modern birds and mammals. Defining the dates of ratite divergences is also critical for determining the age of modern avian orders. To resolve the ratite phylogeny and provide biogeographical data to examine these issues, we have here determined the first complete mitochondrial genome sequences of any extinct taxa--two New Zealand moa genera--along with a 1,000-base-pair sequence from an extinct Madagascan elephant-bird. For comparative data, we also generated 12 kilobases of contiguous sequence from the kiwi, cassowary, emu and two tinamou genera. This large dataset allows statistically precise estimates of molecular divergence dates and these support a Late Cretaceous vicariant speciation of ratite taxa, followed by the subsequent dispersal of the kiwi to New Zealand. This first molecular view of the break-up of Gondwana provides a new temporal framework for speciation events within other Gondwanan biota and can be used to evaluate competing biogeographical hypotheses.

Animals↗
PubMed2001

Evolutionary rate differences in trypanosomes.

Ribosomal RNA-based studies of trypanosome phylogenies have highlighted considerable differences in genetic diversity within clades in the genus Trypanosoma and several-fold substitution rate differences between clades have been identified. While early 18S rRNA-based studies were hampered by highly variable substitution rates and long-branch attraction, it is apparent that genuine differences in evolution rates within localized clades do exist and questions remain regarding what rate or rates such clades are evolving at and why is the application of a single clock to trypanosome evolution so inappropriate? In this study, we explore rate heterogeneity in the commonly used 18S rRNA gene across genus Trypanosoma, using a maximum likelihood (ML) approach to explore local rate variations in clades of biological interest.

Animals↗
PubMed2000

Comparative analyses for adaptive radiations.

Biologists generally agree that most morphological variation between closely related species is adaptive. The most common method of comparative analysis to test for co-evolved character variation is based on a Brownian-motion model of character evolution. If we are to test for the evolution of character-covariation, and we believe that characters have evolved adaptively to fill niches during an adaptive radiation, then it is appropriate to employ appropriate models for character evolution. We show here that under several models of adaptive character evolution and coevolution during an adaptive radiation, which result in closely related species being more similar to each other than to more distantly related species, cross-species analyses are statistically more appropriate than contrast analyses. If the evolution of some traits fits the Brownian-motion model, while others evolve to fill niches during an adaptive radiation, it might be necessary to identify the number of relevant niche dimensions and the modes of character evolution before deciding on appropriate statistical procedures. Alternatively, maximum-likelihood procedures might be used to determine appropriate transformations of phylogenetic branch lengths that accord with particular models of character evolution.

Adaptation, Physiological↗
PubMed2000

Testing the extent of sequence similarity among viroids, satellite RNAs, and hepatitis delta virus.

A Monte Carlo method was used to test the extent of sequence similarity among viroids, satellite RNAs, and hepatitis delta virus. This analysis revealed that there is insufficient sequence similarity among these pathogens to support the hypothesis that they have a common evolutionary origin. Furthermore, while definite patterns of sequence similarity were observed among some viroids, there was a clear lack of overall similarity, indicating that a monophyletic origin for even this group cannot be reliably supported from sequence data alone.

Biological Evolution↗
PubMed2000

The power of relative rates tests depends on the data.

One of the most useful features of molecular phylogenetic analyses is the potential for estimating dates of divergence of evolutionary lineages from the DNA of extant species. But lineage-specific variation in rate of molecular evolution complicates molecular dating, because a calibration rate estimated from one lineage may not be an accurate representation of the rate in other lineages. Many molecular dating studies use a "clock test" to identify and exclude sequences that vary in rate between lineages. However, these clock tests should not be relied upon without a critical examination of their effectiveness at removing rate variable sequences from any given data set, particularly with regard to the sequence length and number of variable sites. As an illustration of this problem we present a power test of a frequently employed triplet relative rates test. We conclude that (1) relative rates tests are unlikely to detect moderate levels of lineage-specific rate variation (where one lineage has a rate of molecular evolution 1.5 to 4.0 times the other) for most commonly used sequences in molecular dating analyses, and (2) this lack of power is likely to result in substantial error in the estimation of dates of divergence. As an example, we show that the well-studied rate difference between murid rodents and great apes will not be detected for many of the sequences used to date the divergence between these two lineages and that this failure to detect rate variation is likely to result in consistent overestimation the date of the rodent-primate split.

Evolution, Molecular↗
PubMed2000

Estimating the rate of molecular evolution: incorporating non-contemporaneous sequences into maximum likelihood phylogenies.

MOTIVATION: TipDate is a program that will use sequences that have been isolated at different dates to estimate their rate of molecular evolution. The program provides a maximum likelihood estimate of the rate and also the associated date of the most recent common ancestor of the sequences, under a model which assumes a constant rate of substitution (molecular clock) but which accommodates the dates of isolation. Confidence intervals for these parameters are also estimated. RESULTS: The approach was applied to a sample of 17 dengue virus serotype 4 sequences, isolated at dates ranging from 1956 to 1994. The rate of substitution for this serotype was estimated to be 7.91 x 10(-4) substitutions per site per year (95% confidence intervals of 6.07 x 10(-4), 9.86 x 10(-4)). This is compatible with a date of 1922 (95% confidence intervals of 1900-1936) for the most recent common ancestor of these sequences. AVAILABILITY: TipDate can be obtained by WWW from http://evolve.zoo. ox.ac.uk/software. The package includes the source code, manual and example files. Both UNIX and Apple Macintosh versions are available from the same site.

DNA, Viral↗
PubMed2000

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

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.

Africa South of the Sahara↗
PubMed1999

Genetic analysis of West Nile New York 1999 encephalitis virus.

Analysis of the genome of the flavivirus responsible for the 1999 New York City encephalitis epidemic cloned from human brain by reverse-transcription polymerase chain reaction Indicates its identity as a lineage I West Nile virus (WNV; WNV-NY1999) closely related to WNVs previously isolated In the Middle East.

Amino Acid Sequence↗
PubMed1999

Widespread intra-serotype recombination in natural populations of dengue virus.

Diversity analysis of 71 published dengue virus gene sequences revealed several strains that appeared to be mosaics comprising gene regions with conflicting evolutionary histories. Subsequent maximum likelihood breakpoint estimation identified seven recombinants, including members of three of the four dengue virus serotypes, with breakpoints in the premembrane/membrane gene, the envelope gene, and at the junction of the envelope and first nonstructural genes. Many of the individual recombinants contain sequence representing separate genetic subtypes. The results were highly statistically significant and were confirmed by phylogenetic analysis of the regions of interest. These findings indicate that recombination may play a very significant role in shaping genetic diversity in dengue virus and, as such, have important implications for its biology and its control.

Dengue Virus↗
PubMed1999

Phylogenetic evidence for recombination in dengue virus.

A split decomposition analysis of dengue (DEN) virus gene sequences revealed extensive networked evolution, indicative of recombination, among DEN-1 strains but not within serotypes DEN-2, DEN-3, or DEN-4. Within DEN-1, two viruses sampled from South America in the last 10 years were identified as recombinants. To map the breakpoints and test their statistical support, we developed a novel maximum likelihood method. In both recombinants, the breakpoints were found to be in similar positions, within the fusion peptide of the envelope protein, demonstrating that a single recombination event occurred prior to the divergence of these two strains. This is the first report of recombination in natural populations of dengue virus.

Dengue↗
PubMed1998

Testing the Cambrian explosion hypothesis by using a molecular dating technique.

Molecular studies have the potential to shed light on the origin of the animal phyla by providing independent estimates of the divergence times, but have been criticized for failing to account adequately for variation in rate of evolution. A method of dating divergence times from molecular data addresses the criticisms of earlier studies and provides more realistic, but wider, confidence intervals. The data are not compatible with the Cambrian explosion hypothesis as an explanation for the origin of metazoan phyla, and provide additional support for an extended period of Precambrian metazoan diversification.

Animals↗
PubMed1998

Estimating divergence dates from molecular sequences.

The ability to date the time of divergence between lineages using molecular data provides the opportunity to answer many important questions in evolutionary biology. However, molecular dating techniques have previously been criticized for failing to adequately account for variation in the rate of molecular evolution. We present a maximum-likelihood approach to estimating divergence times that deals explicitly with the problem of rate variation. This method has many advantages over previous approaches including the following: (1) a rate constancy test excludes data for which rate heterogeneity is detected; (2) date estimates are generated with confidence intervals that allow the explicit testing of hypotheses regarding divergence times; and (3) a range of sequences and fossil dates are used, removing the reliance on a single calculated calibration rate. We present tests of the accuracy of our method, which show it to be robust to the effects of some modes of rate variation. In addition, we test the effect of substitution model and length of sequence on the accuracy of the dating technique. We believe that the method presented here offers solutions to many of the problems facing molecular dating and provides a platform for future improvements to such analyses.

Animals↗