Dataset Information

Assessing constancy of substitution rates in viruses over evolutionary time.

ABSTRACT:

Background

Phylogenetic analyses reveal probable patterns of divergence of present day organisms from common ancestors. The points of divergence of lineages can be dated if a corresponding historical or fossil record exists. For many species, in particular viruses, such records are rare. Recently, Bayesian phylogenetic analysis using sequences from closely related organisms isolated at different times have been used to calibrate divergences. Phylogenetic analyses depend on the assumption that the average substitution rates that can be calculated from the data apply throughout the course of evolution.

Results

The present study tests this crucial assumption by charting the kinds of substitutions observed between pairs of sequences with different levels of total substitutions. Datasets of aligned sequences, both viral and non-viral, were assembled. For each pair of sequences in an aligned set, the distribution of nucleotide interchanges and the total number of changes were calculated. Data were binned according to total numbers of changes and plotted. The accumulation of the six possible interchange types in retroelements as a function of distance followed closely the expected hyperbolic relationship. For other datasets, however, significant deviations from this relationship were noted. A rapid initial accumulation of transition interchanges was frequent among the datasets and anomalous changes occurred at specific divergence levels.

Conclusions

The accumulation profiles suggested that substantial changes in frequencies of types of substitutions occur over the course of evolution and that such changes should be considered in evaluating and dating viral phylogenies.

SUBMITTER: Melcher U

PROVIDER: S-EPMC3026377 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Assessing constancy of substitution rates in viruses over evolutionary time.

Melcher Ulrich U

BMC bioinformatics 20101007

<h4>Background</h4>Phylogenetic analyses reveal probable patterns of divergence of present day organisms from common ancestors. The points of divergence of lineages can be dated if a corresponding historical or fossil record exists. For many species, in particular viruses, such records are rare. Recently, Bayesian phylogenetic analysis using sequences from closely related organisms isolated at different times have been used to calibrate divergences. Phylogenetic analyses depend on the assumption ...[more]

PMID: 20946614

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Project description:BackgroundWhile red blood cell transfusion rates have declined in most Australian medical specialties, obstetric transfusion rates have instead been increasing. Obstetric transfusions are mostly linked to postpartum haemorrhage, the rates of which have also increased over time. This study used two methodological approaches to investigate recent trends in obstetric transfusion in New South Wales (NSW) and the extent to which this was influenced by changing maternal and pregnancy characteristics.MethodsLinked birth and hospital records were used to examine rates of red blood cell transfusion in the postpartum period for mothers giving birth in NSW hospitals from 2005 to 2015. Logistic regression models were run to examine the contribution of maternal and pregnancy risk factors to changing rates of transfusion. Risk factors were divided into "pre-pregnancy" and "pregnancy related". Crude and adjusted estimates of the effect of year of birth on obstetric transfusion rates were compared to assess the effect of risk factors on rates over time using two approaches. The first compared actual and predicted odds ratios of transfusion for each year. The second compared the observed increase in transfusion rate with that predicted after controlling for the risk factors.ResultsAmong 935,659 births, the rate of obstetric transfusion rose from 13 per 1000 births in 2005 to 17 in 2011, and remained stable until 2015. From 2005 to 2015, postpartum haemorrhage increased from 74 to 114 per 1000 births. Compared with the rate in 2005, the available maternal and pregnancy characteristics only partially explained the change in rate of transfusion by 2015 (Method 1, crude odds ratio 1.39 (95% CI 1.25, 1.56); adjusted odds ratio 1.29 (95% CI 1.15, 1.45)). After adjustment for maternal and pregnancy characteristics, obstetric transfusion incidence was predicted to increase by 10.3%, but a 38.7% increase was observed (Method 2).ConclusionRates of obstetric transfusion have stabilised after a period of increase. The trend could not be fully explained by measured maternal and pregnancy characteristics with either of the two approaches. Further investigation of rates and maternal and clinical risk factors will help to inform and improve obstetric blood product use.

Project description:BackgroundSelective pressures at the DNA level shape genes into profiles consisting of patterns of rapidly evolving sites and sites withstanding change. These profiles remain detectable even when protein sequences become extensively diverged. A common task in molecular biology is to infer functional, structural or evolutionary relationships by querying a database using an algorithm. However, problems arise when sequence similarity is low. This study presents an algorithm that uses the evolutionary rate at codon sites, the dN/dS (ω) parameter, coupled to a substitution matrix as an alignment metric for detecting distantly related proteins. The algorithm, called BLOSUM-FIRE couples a newer and improved version of the original FIRE (Functional Inference using Rates of Evolution) algorithm with an amino acid substitution matrix in a dynamic scoring function. The enigmatic hepatitis B virus X protein was used as a test case for BLOSUM-FIRE and its associated database EvoDB.ResultsThe evolutionary rate based approach was coupled with a conventional BLOSUM substitution matrix. The two approaches are combined in a dynamic scoring function, which uses the selective pressure to score aligned residues. The dynamic scoring function is based on a coupled additive approach that scores aligned sites based on the level of conservation inferred from the ω values. Evaluation of the accuracy of this new implementation, BLOSUM-FIRE, using MAFFT alignment as reference alignments has shown that it is more accurate than its predecessor FIRE. Comparison of the alignment quality with widely used algorithms (MUSCLE, T-COFFEE, and CLUSTAL Omega) revealed that the BLOSUM-FIRE algorithm performs as well as conventional algorithms. Its main strength lies in that it provides greater potential for aligning divergent sequences and addresses the problem of low specificity inherent in the original FIRE algorithm. The utility of this algorithm is demonstrated using the Hepatitis B virus X (HBx) protein, a protein of unknown function, as a test case.ConclusionThis study describes the utility of an evolutionary rate based approach coupled to the BLOSUM62 amino acid substitution matrix in inferring protein domain function. We demonstrate that such an approach is robust and performs as well as an array of conventional algorithms.

Dataset Information

Assessing constancy of substitution rates in viruses over evolutionary time.

Background

Results

Conclusions

Publications

Assessing constancy of substitution rates in viruses over evolutionary time.

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