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One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate.

ABSTRACT: The literature is ripe with phylogenetic estimates of nucleotide substitution rates, especially of measurably evolving species such as RNA viruses. However, it is not known how robust these rate estimates are to inaccuracies in the data, particularly in sampling dates that are used for molecular clock calibration. Here we report on the rate of evolution of the emerging pathogen Rabbit hemorrhagic disease virus (RHDV), which has significantly different rates of evolution for the same outer capsid (VP60) gene published in the literature. In an attempt to reconcile the conflicting data and further elucidate details of RHDV?'s evolutionary history, we undertook fresh Bayesian analyses and employed jackknife control methods to produce robust substitution rate and time to most recent common ancestor (TMRCA) estimates for RHDV based on the VP60 and RNA-dependent RNA polymerase genes.Through these control methods, we were able to identify a single misdated taxon, a passaged lab strain used for vaccine production, which was responsible for depressing the RHDV capsid gene's rate of evolution by 65%. Without this isolate, the polymerase and the capsid protein genes had nearly identical rates of evolution: 1.90x10-3 nucleotide substitutions/site/year, ns/s/y, (95% highest probability density (HPD) 1.25x10-3-2.55x10-3) and 1.91x10-3?ns/s/y (95% HPD 1.50x10-3-2.34x10-3), respectively.After excluding the misdated taxon, both genes support a significantly higher substitution rate as well as a relatively recent emergence of RHDV, and obviate the need for previously hypothesized decades of unobserved diversification of the virus. The control methods show that using even one misdated taxon in a large dataset can significantly skew estimates of evolutionary parameters and suggest that it is better practice to use smaller datasets composed of taxa with unequivocal isolation dates. These jackknife controls would be useful for future tip-calibrated rate analyses that include taxa with ambiguous dates of isolation.

SUBMITTER: Hicks AL

PROVIDER: S-EPMC3426481 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate.

Hicks Allison L AL Duffy Siobain S

BMC evolutionary biology 20120530

<h4>Background</h4>The literature is ripe with phylogenetic estimates of nucleotide substitution rates, especially of measurably evolving species such as RNA viruses. However, it is not known how robust these rate estimates are to inaccuracies in the data, particularly in sampling dates that are used for molecular clock calibration. Here we report on the rate of evolution of the emerging pathogen Rabbit hemorrhagic disease virus (RHDV), which has significantly different rates of evolution for th ...[more]

PMID: 22646287

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Project description:BackgroundAnnually, rubella virus (RV) still causes severe congenital defects in around 100 000 children globally. An attempt to eradicate RV is currently underway and analytical tools to monitor the global decline of the last remaining RV lineages will be useful for assessing the effectiveness of this endeavour. RV evolves rapidly enough that much of this information might be inferable from RV genomic sequence data.MethodsUsing BEASTv1.8.0, we analysed publically available RV sequence data to estimate genome-wide and gene-specific nucleotide substitution rates to test whether current estimates of RV substitution rates are representative of the entire RV genome. We specifically accounted for possible confounders of nucleotide substitution rate estimates, such as temporally biased sampling, sporadic recombination, and natural selection favouring either increased or decreased genetic diversity (estimated by the PARRIS and FUBAR methods), at nucleotide sites within the genomic secondary structures (predicted by the NASP method).ResultsWe determine that RV nucleotide substitution rates range from 1.19 × 10(-3) substitutions/site/year in the E1 region to 7.52 × 10(-4) substitutions/site/year in the P150 region. We find that differences between substitution rate estimates in different RV genome regions are largely attributable to temporal sampling biases such that datasets containing higher proportions of recently sampled sequences, will tend to have inflated estimates of mean substitution rates. Although there exists little evidence of positive selection or natural genetic recombination in RV, we show that RV genomes possess pervasive biologically functional nucleic acid secondary structure and that purifying selection acting to maintain this structure contributes substantially to variations in estimated nucleotide substitution rates across RV genomes.ConclusionBoth temporal sampling biases and purifying selection favouring the conservation of RV nucleic acid secondary structures have an appreciable impact on substitution rate estimates but do not preclude the use of RV sequence data to date ancestral sequences. The combination of uniformly high substitution rates across the RV genome and strong temporal structure within the available sequence data, suggests that such data should be suitable for tracking the demographic, epidemiological and movement dynamics of this virus during eradication attempts.

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One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate.

Publications

One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate.

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