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Alexei J Drummond

Publications and source records attributed to Alexei J Drummond.

15 recordsLinked to original sources
PubMed2026

TreeFlow: Probabilistic Modelling and Automatic Differentiation for Phylogenetics.

Probabilistic modelling frameworks are powerful tools for statistical modelling and inference. They are not immediately generalizable to phylogenetic problems due to the particular computational properties of the phylogenetic tree object. TreeFlow is a software library for probabilistic modelling and automatic differentiation with phylogenetic trees. It embeds phylogenetic trees in the TensorFlow Probability framework, and implements inference algorithms for phylogenetic models given a fixed tree topology. We demonstrate how TreeFlow can be used to quickly implement and assess new models. We also show that it provides reasonable performance for gradient-based inference algorithms compared to specialized computational libraries for phylogenetics.

Bayesian inference↗
PubMed2007

Phylogenetic evidence for deleterious mutation load in RNA viruses and its contribution to viral evolution.

Populations of RNA viruses are often characterized by abundant genetic variation. However, the relative fitness of these mutations is largely unknown, although this information is central to our understanding of viral emergence, immune evasion, and drug resistance. Here we develop a phylogenetic method, based on the distribution of nonsynonymous and synonymous changes, to assess the relative fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals that a substantial proportion of the amino acid variation observed in natural populations of RNA viruses comprises transient deleterious mutations that are later purged by purifying selection, potentially limiting virus adaptability. We also demonstrate, for the first time, the existence of a relationship between amino acid variability and the phylogenetic distribution of polymorphisms. From this relationship, we propose an empirical threshold for the maximum viable deleterious mutation load in RNA viruses.

Amino Acid Sequence↗
PubMed2006

Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1.

BACKGROUND: Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear. RESULTS: We use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of the env and gag diversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission. CONCLUSION: Assuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission.

Bayes Theorem↗
PubMed2006

Relaxed phylogenetics and dating with confidence.

In phylogenetics, the unrooted model of phylogeny and the strict molecular clock model are two extremes of a continuum. Despite their dominance in phylogenetic inference, it is evident that both are biologically unrealistic and that the real evolutionary process lies between these two extremes. Fortunately, intermediate models employing relaxed molecular clocks have been described. These models open the gate to a new field of "relaxed phylogenetics." Here we introduce a new approach to performing relaxed phylogenetic analysis. We describe how it can be used to estimate phylogenies and divergence times in the face of uncertainty in evolutionary rates and calibration times. Our approach also provides a means for measuring the clocklikeness of datasets and comparing this measure between different genes and phylogenies. We find no significant rate autocorrelation among branches in three large datasets, suggesting that autocorrelated models are not necessarily suitable for these data. In addition, we place these datasets on the continuum of clocklikeness between a strict molecular clock and the alternative unrooted extreme. Finally, we present analyses of 102 bacterial, 106 yeast, 61 plant, 99 metazoan, and 500 primate alignments. From these we conclude that our method is phylogenetically more accurate and precise than the traditional unrooted model while adding the ability to infer a timescale to evolution.

Animals↗
PubMed2006

A virus reveals population structure and recent demographic history of its carnivore host.

Directly transmitted parasites often provide substantial information about the temporal and spatial characteristics of host-to-host contact. Here, we demonstrate that a fast-evolving virus (feline immunodeficiency virus, FIV) can reveal details of the contemporary population structure and recent demographic history of its natural wildlife host (Puma concolor) that were not apparent from host genetic data and would be impossible to obtain by other means. We suggest that rapidly evolving pathogens may provide a complementary tool for studying population dynamics of their hosts in "shallow" time.

Alberta↗
PubMed2005

Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences.

Although phylogenetic inference of protein-coding sequences continues to dominate the literature, few analyses incorporate evolutionary models that consider the genetic code. This problem is exacerbated by the exclusion of codon-based models from commonly employed model selection techniques, presumably due to the computational cost associated with codon models. We investigated an efficient alternative to standard nucleotide substitution models, in which codon position (CP) is incorporated into the model. We determined the most appropriate model for alignments of 177 RNA virus genes and 106 yeast genes, using 11 substitution models including one codon model and four CP models. The majority of analyzed gene alignments are best described by CP substitution models, rather than by standard nucleotide models, and without the computational cost of full codon models. These results have significant implications for phylogenetic inference of coding sequences as they make it clear that substitution models incorporating CPs not only are a computationally realistic alternative to standard models but may also frequently be statistically superior.

Classification↗
PubMed2005

Tree measures and the number of segregating sites in time-structured population samples.

BACKGROUND: Time-structured genetic samples are a valuable source of information in population genetics because they provide several correlated observations of the underlying evolutionary processes. In this paper we study basic properties of the genetic variation in time-structured samples as reflected in the genealogies relating individuals and the number of segregating sites observed. Our emphasis is on "measurably evolving populations" i.e. populations from which it is possible to obtain time-structured samples that span a significant interval of evolutionary time. RESULTS: We use results from the coalescent process to derive properties of time-structured samples. In the first section we extend existing results to attain measures on coalescent trees relating time-structured samples. These include the expected time to a most recent common ancestor, the expected total branch length and the expected length of branches subtending only ancient individuals. The effect of different sampling schemes on the latter measure is studied. In the second section we study the special case where the full sample consists of a group of contemporary extant samples and a group of contemporary ancient samples. As regards this case, we present results and applications concerning the probability distribution of the number of segregating sites where a mutation is unique to the ancient individuals and the number of segregating sites where a mutation is shared between ancient and extant individuals. CONCLUSION: The methodology and results presented here is of use to the design and interpretation of ancient DNA experiments. Furthermore, the results may be useful in further development of statistical tests of e.g. population dynamics and selection, which include temporal information.

Animals↗
PubMed2005

Molecular phylogeny of coleoid cephalopods (Mollusca: Cephalopoda) using a multigene approach; the effect of data partitioning on resolving phylogenies in a Bayesian framework.

The resolution of higher level phylogeny of the coleoid cephalopods (octopuses, squids, and cuttlefishes) has been hindered by homoplasy among morphological characters in conjunction with a very poor fossil record. Initial molecular studies, based primarily on small fragments of single mitochondrial genes, have produced little resolution of the deep relationships amongst coleoid cephalopod families. The present study investigated this issue using 3415 base pairs (bp) from three nuclear genes (octopine dehydrogenase, pax-6, and rhodopsin) and three mitochondrial genes (12S rDNA, 16S rDNA, and cytochrome oxidase I) from a total of 35 species (including representatives of each of the higher level taxa). Bayesian analyses were conducted on mitochondrial and nuclear genes separately and also all six genes together. Separate analyses were conducted with the data partitioned by gene, codon/rDNA, gene+codon/rDNA or not partitioned at all. In the majority of analyses partitioning the data by gene+codon was the appropriate model with partitioning by codon the second most selected model. In some instances the topology varied according to the model used. Relatively high posterior probabilities and high levels of congruence were present between the topologies resulting from the analysis of all Octopodiform (octopuses and vampire "squid") taxa for all six genes, and independently for the datasets of mitochondrial and nuclear genes. In contrast, the highest levels of resolution within the Decapodiformes (squids and cuttlefishes) resulted from analysis of nuclear genes alone. Different higher level Decapodiform topologies were obtained through the analysis of only the 1st+2nd codon positions of nuclear genes and of all three codon positions. It is notable that there is strong evidence of saturation among the 3rd codon positions within the Decapodiformes and this may contribute spurious signal. The results suggest that the Decapodiformes may have radiated earlier and/or had faster rates of evolution than the Octopodiformes. The following taxonomic conclusions are drawn from our analyses: (1) the order Octopoda and suborders Cirrata, Incirrata, and Oegopsida are monophyletic groups; (2) the family Spirulidae (Ram's horn squids) are the sister taxon to the family Sepiidae (cuttlefishes); (3) the family Octopodidae, as currently defined, is paraphyletic; (4) the superfamily Argonautoidea are basal within the suborder Incirrata; and (5) the benthic octopus genera Benthoctopus and Enteroctopus are sister taxa.

Animals↗
PubMed2005

Time dependency of molecular rate estimates and systematic overestimation of recent divergence times.

Studies of molecular evolutionary rates have yielded a wide range of rate estimates for various genes and taxa. Recent studies based on population-level and pedigree data have produced remarkably high estimates of mutation rate, which strongly contrast with substitution rates inferred in phylogenetic (species-level) studies. Using Bayesian analysis with a relaxed-clock model, we estimated rates for three groups of mitochondrial data: avian protein-coding genes, primate protein-coding genes, and primate d-loop sequences. In all three cases, we found a measurable transition between the high, short-term (< 1-2 Myr) mutation rate and the low, long-term substitution rate. The relationship between the age of the calibration and the rate of change can be described by a vertically translated exponential decay curve, which may be used for correcting molecular date estimates. The phylogenetic substitution rates in mitochondria are approximately 0.5% per million years for avian protein-coding sequences and 1.5% per million years for primate protein-coding and d-loop sequences. Further analyses showed that purifying selection offers the most convincing explanation for the observed relationship between the estimated rate and the depth of the calibration. We rule out the possibility that it is a spurious result arising from sequence errors, and find it unlikely that the apparent decline in rates over time is caused by mutational saturation. Using a rate curve estimated from the d-loop data, several dates for last common ancestors were calculated: modern humans and Neandertals (354 ka; 222-705 ka), Neandertals (108 ka; 70-156 ka), and modern humans (76 ka; 47-110 ka). If the rate curve for a particular taxonomic group can be accurately estimated, it can be a useful tool for correcting divergence date estimates by taking the rate decay into account. Our results show that it is invalid to extrapolate molecular rates of change across different evolutionary timescales, which has important consequences for studies of populations, domestication, conservation genetics, and human evolution.

Animals↗
PubMed2005

Accuracy of rate estimation using relaxed-clock models with a critical focus on the early metazoan radiation.

In recent years, a number of phylogenetic methods have been developed for estimating molecular rates and divergence dates under models that relax the molecular clock constraint by allowing rate change throughout the tree. These methods are being used with increasing frequency, but there have been few studies into their accuracy. We tested the accuracy of several relaxed-clock methods (penalized likelihood and Bayesian inference using various models of rate change) using nucleotide sequences simulated on a nine-taxon tree. When the sequences evolved with a constant rate, the methods were able to infer rates accurately, but estimates were more precise when a molecular clock was assumed. When the sequences evolved under a model of auto-correlated rate change, rates were accurately estimated using penalized likelihood and by Bayesian inference using lognormal and exponential models of rate change, while other models did not perform as well. When the sequences evolved under a model of uncorrelated rate change, only Bayesian inference using an exponential rate model performed well. Collectively, the results provide a strong recommendation for using the exponential model of rate change if a conservative approach to divergence time estimation is required. A case study is presented in which we use a simulation-based approach to examine the hypothesis of elevated rates in the Cambrian period, and it is found that these high rate estimates might be an artifact of the rate estimation method. If this bias is present, then the ages of metazoan divergences would be systematically underestimated. The results of this study have implications for studies of molecular rates and divergence dates.

Algorithms↗
PubMed2004

Rise and fall of the Beringian steppe bison.

The widespread extinctions of large mammals at the end of the Pleistocene epoch have often been attributed to the depredations of humans; here we present genetic evidence that questions this assumption. We used ancient DNA and Bayesian techniques to reconstruct a detailed genetic history of bison throughout the late Pleistocene and Holocene epochs. Our analyses depict a large diverse population living throughout Beringia until around 37,000 years before the present, when the population's genetic diversity began to decline dramatically. The timing of this decline correlates with environmental changes associated with the onset of the last glacial cycle, whereas archaeological evidence does not support the presence of large populations of humans in Eastern Beringia until more than 15,000 years later.

Alaska↗
PubMed2004

Ancient DNA: would the real Neandertal please stand up?

Mitochondrial DNA sequences recovered from eight Neandertal specimens cannot be detected in either early fossil Europeans or in modern populations. This indicates that, if Neandertals made any genetic contribution at all to modern humans, it must have been limited, though the extent of the contribution cannot be resolved at present.

Animals↗
PubMed2004

The molecular population genetics of HIV-1 group O.

HIV-1 group O originated through cross-species transmission of SIV from chimpanzees to humans and has established a relatively low prevalence in Central Africa. Here, we infer the population genetics and epidemic history of HIV-1 group O from viral gene sequence data and evaluate the effect of variable evolutionary rates and recombination on our estimates. First, model selection tools were used to specify suitable evolutionary and coalescent models for HIV group O. Second, divergence times and population genetic parameters were estimated in a Bayesian framework using Markov chain Monte Carlo sampling, under both strict and relaxed molecular clock methods. Our results date the origin of the group O radiation to around 1920 (1890-1940), a time frame similar to that estimated for HIV-1 group M. However, group O infections, which remain almost wholly restricted to Cameroon, show a slower rate of exponential growth during the twentieth century, explaining their lower current prevalence. To explore the effect of recombination, the Bayesian framework is extended to incorporate multiple unlinked loci. Although recombination can bias estimates of the time to the most recent common ancestor, this effect does not appear to be important for HIV-1 group O. In addition, we show that evolutionary rate estimates for different HIV genes accurately reflect differential selective constraints along the HIV genome.

Bayes Theorem↗
PubMed2002

Estimating mutation parameters, population history and genealogy simultaneously from temporally spaced sequence data.

Molecular sequences obtained at different sampling times from populations of rapidly evolving pathogens and from ancient subfossil and fossil sources are increasingly available with modern sequencing technology. Here, we present a Bayesian statistical inference approach to the joint estimation of mutation rate and population size that incorporates the uncertainty in the genealogy of such temporally spaced sequences by using Markov chain Monte Carlo (MCMC) integration. The Kingman coalescent model is used to describe the time structure of the ancestral tree. We recover information about the unknown true ancestral coalescent tree, population size, and the overall mutation rate from temporally spaced data, that is, from nucleotide sequences gathered at different times, from different individuals, in an evolving haploid population. We briefly discuss the methodological implications and show what can be inferred, in various practically relevant states of prior knowledge. We develop extensions for exponentially growing population size and joint estimation of substitution model parameters. We illustrate some of the important features of this approach on a genealogy of HIV-1 envelope (env) partial sequences.

Decision Trees↗