Department of Microbial Ecology, The Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands.
Laboratory of Virology, Wageningen University and Research, Wageningen, The Netherlands.
PLoS Genet. 2022 Jun 6;18(6):e1009806. doi: 10.1371/journal.pgen.1009806. eCollection 2022 Jun.
Mutation rates are of key importance for understanding evolutionary processes and predicting their outcomes. Empirical mutation rate estimates are available for a number of RNA viruses, but few are available for DNA viruses, which tend to have larger genomes. Whilst some viruses have very high mutation rates, lower mutation rates are expected for viruses with large genomes to ensure genome integrity. Alphabaculoviruses are insect viruses with large genomes and often have high levels of polymorphism, suggesting high mutation rates despite evidence of proofreading activity by the replication machinery. Here, we report an empirical estimate of the mutation rate per base per strand copying (s/n/r) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). To avoid biases due to selection, we analyzed mutations that occurred in a stable, non-functional genomic insert after five serial passages in Spodoptera exigua larvae. Our results highlight that viral demography and the stringency of mutation calling affect mutation rate estimates, and that using a population genetic simulation model to make inferences can mitigate the impact of these processes on estimates of mutation rate. We estimated a mutation rate of μ = 1×10-7 s/n/r when applying the most stringent criteria for mutation calling, and estimates of up to μ = 5×10-7 s/n/r when relaxing these criteria. The rates at which different classes of mutations accumulate provide good evidence for neutrality of mutations occurring within the inserted region. We therefore present a robust approach for mutation rate estimation for viruses with stable genomes, and strong evidence of a much lower alphabaculovirus mutation rate than supposed based on the high levels of polymorphism observed.
突变率对于理解进化过程和预测其结果至关重要。已经有许多 RNA 病毒的经验突变率估计，但 DNA 病毒的估计很少，因为它们的基因组往往更大。虽然有些病毒的突变率非常高，但对于具有大基因组的病毒，较低的突变率有望确保基因组的完整性。α杆状病毒是具有大基因组的昆虫病毒，通常具有高水平的多态性，这表明尽管复制机制存在校对活性，但突变率仍然很高。在这里，我们报告了 Autographa californica 多粒包埋核型多角体病毒（AcMNPV）每碱基每链复制（s/n/r）的经验突变率估计。为了避免由于选择而产生的偏差，我们分析了在 Spodoptera exigua 幼虫中连续传代五次后发生在稳定的非功能基因组插入物中的突变。我们的结果强调了病毒种群动态和突变调用的严格性会影响突变率估计，并且使用群体遗传模拟模型进行推断可以减轻这些过程对突变率估计的影响。当应用最严格的突变调用标准时，我们估计μ = 1×10-7 s/n/r 的突变率，而当放宽这些标准时，估计值高达μ = 5×10-7 s/n/r。不同类别的突变积累的速率为插入区域内发生的突变的中性提供了很好的证据。因此，我们提出了一种用于具有稳定基因组的病毒的突变率估计的稳健方法，并提供了强有力的证据表明，与观察到的高水平多态性相比，α杆状病毒的突变率要低得多。
