COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral genome is considered to be relatively stable and the mutations that have been observed and reported thus far are mainly focused on the coding region. This article provides evidence that macrolevel pandemic dynamics, such as social distancing, modulate the genomic evolution of SARS-CoV-2. This view complements the prevalent paradigm that microlevel observables control macrolevel parameters such as death rates and infection patterns. First, we observe differences in mutational signals for geospatially separated populations such as the prevalence of A23404G in CA versus NY and WA. We show that the feedback between macrolevel dynamics and the viral population can be captured employing a transfer entropy framework. Second, we observe complex interactions within mutational clades. Namely, when C14408T first appeared in the viral population, the frequency of A23404G spiked in the subsequent week. Third, we identify a noncoding mutation, G29540A, within the segment between the coding gene of the N protein and the ORF10 gene, which is largely confined to NY (95%). These observations indicate that macrolevel sociobehavioral measures have an impact on the viral genomics and may be useful for the dashboard-like tracking of its evolution. Finally, despite the fact that SARS-CoV-2 is a genetically robust organism, our findings suggest that we are dealing with a high degree of adaptability. Owing to its ample spread, mutations of unusual form are observed and a high complexity of mutational interaction is exhibited.

中文翻译：

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SARS-CoV-2病毒进化中的多尺度反馈环

COVID-19是一种由严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）引起的传染病。病毒基因组被认为是相对稳定的，迄今已观察和报道的突变主要集中在编码区。本文提供的证据表明，大范围的流行病动态（例如社会距离）可以调节SARS-CoV-2的基因组进化。这种观点补充了微观观察者控制宏观水平参数（例如死亡率和感染模式）的普遍范例。首先，我们观察到了地理空间上分离的群体的突变信号的差异，例如CA与NY和WA在A23404G的患病率。我们表明，可以使用转移熵框架来捕获宏观动力学与病毒种群之间的反馈。第二，我们观察到突变进化枝内的复杂相互作用。即，当C14408T首次出现在病毒种群中时，A23404G的频率在随后的一周内达到峰值。第三，我们在N蛋白的编码基因和ORF10基因之间的片段中鉴定出一个非编码突变G29540A，该突变主要限于NY（95％）。这些观察结果表明，宏观的社会行为学措施对病毒基因组学有影响，并且可能对于仪表板式的病毒进化跟踪很有用。最后，尽管SARS-CoV-2是一种遗传上强健的生物，但我们的发现表明我们正在应对高度的适应性。由于其充分的传播，观察到不寻常形式的突变，并且显示出突变相互作用的高度复杂性。