Neher Richard A
Biozentrum, University of Basel, Spitalstrasse 41, Basel 4053, Switzerland.
Swiss Institute of Bioinformatics, Spitalstrasse 41, Basel 4053, Switzerland.
Virus Evol. 2022 Dec 10;8(2):veac113. doi: 10.1093/ve/veac113. eCollection 2022.
Continued evolution and adaptation of SARS-CoV-2 has led to more transmissible and immune-evasive variants with profound impacts on the course of the pandemic. Here I analyze the evolution of the virus over 2.5 years since its emergence and estimate the rates of evolution for synonymous and non-synonymous changes separately for evolution within clades-well-defined monophyletic groups with gradual evolution-and for the pandemic overall. The rate of synonymous mutation is found to be around 6 changes per year. Synonymous rates within variants vary little from variant to variant and are compatible with the overall rate of 7 changes per year (or [Formula: see text] per year and codon). In contrast, the rate at which variants accumulate amino acid changes (non-synonymous mutations) was initially around 12-16 changes per year, but in 2021 and 2022 it dropped to 6-9 changes per year. The overall rate of non-synonymous evolution, that is across variants, is estimated to be about 26 amino acid changes per year (or [Formula: see text] per year and codon). This strong acceleration of the overall rate compared to within clade evolution indicates that the evolutionary process that gave rise to the different variants is qualitatively different from that in typical transmission chains and likely dominated by adaptive evolution. I further quantify the spectrum of mutations and purifying selection in different SARS-CoV-2 proteins and show that the massive global sampling of SARS-CoV-2 is sufficient to estimate site-specific fitness costs across the entire genome. Many accessory proteins evolve under limited evolutionary constraints with little short-term purifying selection. About half of the mutations in other proteins are strongly deleterious.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的持续进化和适应导致了更具传播性和免疫逃逸性的变体，对疫情发展产生了深远影响。在此，我分析了该病毒自出现以来2.5年的进化情况，并分别估算了进化枝（定义明确的单系类群，具有渐进进化）内进化以及整体疫情中同义突变和非同义突变的进化速率。同义突变率约为每年6次变化。不同变体间的同义突变率差异不大，与每年7次变化（或每年每密码子[公式：见原文]）的总体速率相符。相比之下，变体积累氨基酸变化（非同义突变）的速率最初约为每年12 - 16次变化，但在2021年和2022年降至每年6 - 9次变化。跨变体的非同义进化总体速率估计约为每年26个氨基酸变化（或每年每密码子[公式：见原文]）。与进化枝内进化相比，总体速率的这种强烈加速表明，产生不同变体的进化过程在性质上不同于典型传播链中的进化过程，可能以适应性进化为主导。我进一步量化了不同SARS-CoV-2蛋白中的突变谱和纯化选择，并表明对SARS-CoV-2进行大规模全球采样足以估计整个基因组中位点特异性的适应度成本。许多辅助蛋白在有限的进化限制下进化，短期纯化选择很少。其他蛋白中约一半的突变是严重有害的。
