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Biomedical subjects

V Moulton

Publications and source records attributed to V Moulton.

9 recordsLinked to original sources
PubMed2001

Pruned median networks: a technique for reducing the complexity of median networks.

Observations from molecular marker studies on recently diverged species indicate that substitution patterns in DNA sequences can often be complex and poorly described by tree-like bifurcating evolutionary models. These observations might result from processes of species diversification and/or processes of sequence evolution that are not tree-like. In these cases, bifurcating tree representations provide poor visualization of phylogenetic signals in sequence data. In this paper, we use median networks to study DNA sequence substitution patterns in plant nuclear and chloroplast markers. We describe how to prune median networks to obtain so called pruned median networks. These simpler networks may help to provide a useful framework for investigating the phylogenetic complexity of recently diverged taxa with hybrid origins.

Base Sequence↗
PubMed2000

Use of RNA secondary structure for studying the evolution of RNase P and RNase MRP.

Secondary structure is evaluated for determining evolutionary relationships between catalytic RNA molecules that are so distantly related they are scarcely alignable. The ribonucleoproteins RNase P (P) and RNase MRP (MRP) have been suggested to be evolutionarily related because of similarities in both function and secondary structure. However, their RNA sequences cannot be aligned with any confidence, and this leads to uncertainty in any trees inferred from sequences. We report several approaches to using secondary structures for inferring evolutionary trees and emphasize quantitative tests to demonstrate that evolutionary information can be recovered. For P and MRP, three hypotheses for the relatedness are considered. The first is that MRP is derived from P in early eukaryotes. The next is that MRP is derived from P from an early endosymbiont. The third is that both P and MRP evolved in the RNA-world (and the need for MRP has since been lost in prokaryotes). Quantitative comparisons of the pRNA and mrpRNA secondary structures have found that the possibility of an organellar origin of MRP is unlikely. In addition, comparison of secondary structures support the identity of an RNase P-like sequence in the maize chloroplast genome. Overall, it is concluded that RNA secondary structure is useful for evaluating evolutionary relatedness, even with sequences that cannot be aligned with confidence.

Animals↗
PubMed2000

RNA folding argues against a hot-start origin of life.

Opinion is strongly divided on whether life arose on earth under hot or cold conditions, the hot-start and cold-start scenarios, respectively. The origin of life close to deep thermal vents appears as the majority opinion among biologists, but there is considerable biochemical evidence that high temperatures are incompatible with an RNA world. To be functional, RNA has to fold into a three-dimensional structure. We report both theoretical and experimental results on RNA folding and show that (as expected) hot conditions strongly reduce RNA folding. The theoretical results come from energy-minimization calculations of the average extent of folding of RNA, mainly from 0-90 degrees C, for both random sequences and tRNA sequences. The experimental results are from circular-dichroism measurements of tRNA over a similar range of temperatures. The quantitative agreement between calculations and experiment is remarkable, even to the shape of the curves indicating the cooperative nature of RNA folding and unfolding. These results provide additional evidence for a lower temperature stage being necessary in the origin of life.

Hot Temperature↗
PubMed2000

Likelihood analysis of phylogenetic networks using directed graphical models.

A method for computing the likelihood of a set of sequences assuming a phylogenetic network as an evolutionary hypothesis is presented. The approach applies directed graphical models to sequence evolution on networks and is a natural generalization of earlier work by Felsenstein on evolutionary trees, including it as a special case. The likelihood computation involves several steps. First, the phylogenetic network is rooted to form a directed acyclic graph (DAG). Then, applying standard models for nucleotide/amino acid substitution, the DAG is converted into a Bayesian network from which the joint probability distribution involving all nodes of the network can be directly read. The joint probability is explicitly dependent on branch lengths and on recombination parameters (prior probability of a parent sequence). The likelihood of the data assuming no knowledge of hidden nodes is obtained by marginalization, i.e., by summing over all combinations of unknown states. As the number of terms increases exponentially with the number of hidden nodes, a Markov chain Monte Carlo procedure (Gibbs sampling) is used to accurately approximate the likelihood by summing over the most important states only. Investigating a human T-cell lymphotropic virus (HTLV) data set and optimizing both branch lengths and recombination parameters, we find that the likelihood of a corresponding phylogenetic network outperforms a set of competing evolutionary trees. In general, except for the case of a tree, the likelihood of a network will be dependent on the choice of the root, even if a reversible model of substitution is applied. Thus, the method also provides a way in which to root a phylogenetic network by choosing a node that produces a most likely network.

Computer Graphics↗
PubMed2000

Evolutionary rate and genetic drift of hepatitis C virus are not correlated with the host immune response: studies of infected donor-recipient clusters.

Six donor-recipient clusters of hepatitis C virus (HCV)-infected individuals were studied. For five clusters the period of infection of the donor could be estimated, and for all six clusters the time of infection of the recipients from the donor via blood transfusion was also precisely known. Detailed phylogenetic analyses were carried out to investigate the genomic evolution of the viral quasispecies within infected individuals in each cluster. The molecular clock analysis showed that HCV quasispecies within a patient are evolving at the same rate and that donors that have been infected for longer time tend to have a lower evolutionary rate. Phylogenetic analysis based on the split decomposition method revealed different evolutionary patterns in different donor-recipient clusters. Reactivity of antibody against the first hypervariable region (HVR1) of HCV in donor and recipient sera was evaluated and correlated to the calculated evolutionary rate. Results indicate that anti-HVR1 reactivity was related more to the overall level of humoral immune response of the host than to the HVR1 sequence itself, suggesting that the particular sequence of the HVR1 peptides is not the determinant of reactivity. Moreover, no correlation was found between the evolutionary rate or the heterogeneity of the viral quasispecies in the patients and the strength of the immune response to HVR1 epitopes. Rather, the results seem to imply that genetic drift is less dependent on immune pressure than on the rate of evolution and that the genetic drift of HCV is independent of the host immune pressure.

Blood Donors↗
PubMedDate not supplied

Metrics on RNA secondary structures.

Many different programs have been developed for the prediction of the secondary structure of an RNA sequence. Some of these programs generate an ensemble of structures, all of which have free energy close to that of the optimal structure, making it important to be able to quantify how similar these different structures are. To deal with this problem, we define a new class of metrics, the mountain metrics, on the set of RNA secondary structures of a fixed length. We compare properties of these metrics with other well known metrics on RNA secondary structures. We also study some global and local properties of these metrics.

Biometry↗