One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate.
One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate.
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DOI：
10.1186/1471-2148-12-74
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发表时间：
2012-05-30
影响因子：
3.4
通讯作者：
Duffy S
中科院分区：
文献类型：
--
作者：
Hicks AL;Duffy S
文献中对核苷酸取代率的系统发育估计是成熟的，特别是对可测量的进化物种，如RNA病毒。然而，目前尚不清楚这些速率估计对数据的不准确性，特别是用于分子钟校准的采样日期有多可靠。本文报道了新发病原体兔出血症病毒（RHDV）的进化速度，这两种病毒对同一外衣壳（VP60）基因的进化速度在文献中有显著差异。为了调和相互矛盾的数据并进一步阐明RHDV进化史的细节，我们进行了新的贝叶斯分析，并采用折刀控制方法，基于VP60和RNA依赖的RNA聚合酶基因，对RHDV进行了可靠的替代率和到最近共同祖先（TMRCA）的时间估计。通过这些控制方法，我们能够确定一个错误的分类群，一个用于疫苗生产的传代实验室菌株，它负责将RHDV衣壳基因的进化速率降低65%。没有该分离物，聚合酶和衣壳蛋白基因的进化速率几乎相同：1.90 × 10-3个核苷酸取代/位点/年，ns/s/y（95%最高概率密度（HPD）分别为1.25x10-3-2.55x10-3）和1.91x10-3 ns/s/y （95% HPD为1.50x10-3-2.34x10-3）。在排除了错误的分类群之后，这两个基因都支持明显更高的替代率，以及相对较新的RHDV出现，并消除了先前假设的数十年未观察到的病毒多样化的需要。控制方法表明，即使在一个大数据集中使用一个错误的分类单元，也会显著扭曲进化参数的估计，并建议使用由具有明确分离日期的分类单元组成的较小数据集。这些折刀控制将有助于未来的尖端校准率分析，包括分离日期不明确的分类群。
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.