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A Rambaut

Publications and source records attributed to A Rambaut.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1997

Elucidating the population histories and transmission dynamics of papillomaviruses using phylogenetic trees.

Using gene genealogies constructed from gene sequence data, we show that both the mucosal and cutaneous papillomaviruses (PV)-supergroups A and B-appear to have been transmitted through susceptible populations faster than exponentially. The data and methods involved (1) examining the PV database for phylogenetic signal in an L1 open reading frame (ORF) fragment and an E1 ORF segment, (2) demonstrating that the same two fragments have evolved in a way consistent with a molecular clock, and (3) applying methods of phylogenetic tree analysis that test different scenarios for the dynamics of viral transmission within populations. The results indicate increases in PV populations of both supergroups A and B in the recent past. This form of the increases, which fit a null model of population growth with an exponent increasing in time, is compatible with the fact that human populations have grown at a faster than exponential rate, thus increasing the numbers of susceptible hosts for HPVs. There are, however, indications that the population of supergroup A has now stopped increasing in size.

Codon↗
PubMed1997

Seq-Gen: an application for the Monte Carlo simulation of DNA sequence evolution along phylogenetic trees.

MOTIVATION: Seq-Gen is a program that will simulate the evolution of nucleotide sequences along a phylogeny, using common models of the substitution process. A range of models of molecular evolution are implemented, including the general reversible model. Nucleotide frequencies and other parameters of the model may be given and site-specific rate heterogeneity can also be incorporated in a number of ways. Any number of trees may be read in and the program will produce any number of data sets for each tree. Thus, large sets of replicate simulations can be easily created. This can be used to test phylogenetic hypotheses using the parametric bootstrap. AVAILABILITY: Seq-Gen can be obtained by WWW from http:/(/)evolve.zoo.ox.ac.uk/Seq-Gen/seq-gen.html++ + or by FTP from ftp:/(/)evolve.zoo.ox.ac.uk/packages/Seq-Gen/. The package includes the source code, manual and example files. An Apple Macintosh version is available from the same sites.

Algorithms↗
PubMed1997

End-Epi: an application for inferring phylogenetic and population dynamical processes from molecular sequences.

MOTIVATION: Phylogenetic trees constructed from molecular sequences contain information about the evolutionary or population dynamical processes that created them. Here we describe a computer package (End-Epi) that uses graphical methods to allow researchers to make inferences about these processes from their data. Statistical analyses can be performed to test the consistency of the data with various competing hypotheses. AVAILABILITY: End-Epi can be obtained by WWW from http://evolve.zoo.ox.ac.uk/ and by anonymous FTP from ftp://evolve.zoo.ox.ac.uk/packages/End-Epi10.hqx. This file contains the compiled application, the manual and a test tree.

Algorithms↗
PubMed1996

Inferring the population history of an epidemic from a phylogenetic tree.

Phylogenetic or family trees reconstructed from a sample of individuals belonging to a population or species can be used to infer population dynamic history. A method for making such inferences involves visual inspection of the graphs of the numbers of lineages in the phylogeny plotted against the times when they occur. One transformation of the lineages axis often produces a linear lineages-through-time plot if the population has been growing exponentially. However, that transformation is known to fail under certain circumstances. We report a series of simulation studies designed to determine the conditions under which the transformation fails. As long as the sample represents less than 0.5% of individuals in the total population, the Type 1 error rate is acceptable. This means that studies of virus populations are likely not to suffer from transformation failure, so long as a random sample from the population is represented. When the transformation does fail, the resultant lineages-through-time plot is very similar to a two-stage epidemic process.

Computer Simulation↗
PubMed1996

Isolation and sequence analysis of a cDNA encoding the c subunit of a vacuolar-type H(+)-ATPase from the CAM plant Kalanchoë daigremontiana.

We report the sequence of a cDNA clone encoding the c ("16 kDa') subunit of a vacuolar-type H(+)-ATPase (V-ATPase) from Kalanchoë daigremontiana, a plant in which the cell vacuole plays a pivotal role in crassulacean acid metabolism. The clone, pKVA211, was isolated from a K. daigremontiana leaf cDNA library constructed in lambda ZAP II using a homologous PCR-generated cDNA probe for the V-ATPase c subunit. The KVA211 cDNA was 839 nucleotides long and included a 20 bp poly(A)+ tail together with a complete 495 bp coding region for a polypeptide with a predicted molecular mass of 16659 Da. The deduced amino acid sequence was highly conserved across the wide range of eukaryotes (vertebrates, invertebrates, fungi, plants and protozoa) in which this gene has now been identified. Sequence comparison of several PCR products and genomic Southern analysis indicated that the V-ATPase c subunit in K. daigremontiana is encoded by a small multi-gene family. Steady-state levels of the KVA211 mRNA were much higher in leaves than in roots or flowers, and expression of this transcript in leaves was shown to be strongly light-dependent.

Amino Acid Sequence↗
PubMed1996

Recombination between sequences of hepatitis B virus from different genotypes.

A comparison of 25 hepatitis B virus (HBV) isolates for which complete genome sequences are available revealed two that occupied different positions in phylogenetic trees reconstructed from different open reading frames. Further analysis indicated that this incongruence was the result of recombination between viruses of different genomic and antigenic types. Both putative recombinants originated from geographic regions where multiple genotypes are known to cocirculate. A search of the sequence databases showed evidence of similar intergenotypic recombinants. These observations indicate that recombination between divergent strains may represent an important source of genetic variation in HBV.

Evolution, Molecular↗
PubMed1996

Determinants of rate variation in mammalian DNA sequence evolution.

Attempts to analyze variation in the rates of molecular evolution among mammalian lineages have been hampered by paucity of data and by nonindependent comparisons. Using phylogenetically independent comparisons, we test three explanations for rate variation which predict correlations between rate variation and generation time, metabolic rate, and body size. Mitochondrial and nuclear genes, protein coding, rRNA, and nontranslated sequences from 61 mammal species representing 14 orders are used to compare the relative rates of sequence evolution. Correlation analyses performed on differences in genetic distance since common origin of each pair against differences in body mass, generation time, and metabolic rate reveal that substitution rate at fourfold degenerate sites in two out of three protein sequences is negatively correlated with generation time. In addition, there is a relationship between the rate of molecular evolution and body size for two nuclear-encoded sequences. No evidence is found for an effect of metabolic rate on rate of sequence evolution. Possible causes of variation in substitution rate between species are discussed.

Age Factors↗
PubMed1996

Bi-De: an application for simulating phylogenetic processes.

Birth-Death (Bi-De) is an application for the Apple Macintosh which simulates the growth of phylogenetic trees using various models of lineage birth and death. The trees produced are intended to be analogous to those reconstructed from molecular sequence data. The user may define a constant birth rate and death rate or a function describing how these rates vary by time or population size. Instantaneous mass extinctions can also be simulated. The package allows the tree produced to be used as a template for the simulated evolution of molecular sequence data under a range of different transition models.

Algorithms↗
PubMed1996

Complete nucleotide sequence and transcriptional analysis of snakehead fish retrovirus.

The complete genome of the snakehead fish retrovirus has been cloned and sequenced, and its transcriptional profile in cell culture has been determined. The 11.2-kb provirus displays a complex expression pattern capable of encoding accessory proteins and is unique in the predicted location of the env initiation codon and signal peptide upstream of gag and the common splice donor site. The virus is distinguishable from all known retrovirus groups by the presence of an arginine tRNA primer binding site. The coding regions are highly divergent and show a number of unusual characteristics, including a large Gag coiled-coil region, a Pol domain of unknown function, and a long, lentiviral-like, Env cytoplasmic domain. Phylogenetic analysis of the Pol sequence emphasizes the divergent nature of the virus from the avian and mammalian retroviruses. The snakehead virus is also distinct from a previously characterized complex fish retrovirus, suggesting that discrete groups of these viruses have yet to be identified in the lower vertebrates.

Amino Acid Sequence↗
PubMed1995

Inferring population history from molecular phylogenies.

Variable molecular sequences sampled from a population can be used to infer its dynamic history. Graphical methods are developed and applied to real data, illustrating ways of navigating through hypothesis space with two landmarks for reference: constant population size and exponentially growing population size.

Genetics, Population↗