VanInsberghe David, Neish Andrew S, Lowen Anice C, Koelle Katia
Department of Pathology, Emory University, Atlanta, GA, USA.
Department of Biology, Emory University, Atlanta, GA, USA.
bioRxiv. 2021 Mar 15:2020.08.05.238386. doi: 10.1101/2020.08.05.238386.
Viral recombination can generate novel genotypes with unique phenotypic characteristics, including transmissibility and virulence. Although the capacity for recombination among betacoronaviruses is well documented, there is limited evidence of recombination between SARS-CoV-2 strains. By identifying the mutations that primarily determine SARS-CoV-2 clade structure, we developed a lightweight approach for detecting recombinant genomes. Among the over 537,000 genomes queried, we detect 1175 putative recombinants that contain multiple mutational markers from distinct clades. Additional phylogenetic analysis and the observed co-circulation of predicted parent clades in the geographic regions of exposure further support the feasibility of recombination in these detected cases. An analysis of these detected cases did not reveal any evidence for recombination hotspots in the SARS-CoV-2 genome. Although most recombinant genotypes were detected a limited number of times, at least two recombinants are now widely transmitted. Recombinant genomes were also found to contain substitutions of concern for elevated transmissibility and lower vaccine efficacy, including D614G, N501Y, E484K, and L452R. Adjusting for an unequal probability of detecting recombinants derived from different parent clades, and for geographic variation in clade abundance, we estimate that at most 5% of circulating viruses in the USA and UK are recombinant. While the phenotypic characterization of detected recombinants was beyond the scope of our analysis, the identification of transmitted recombinants involving substitutions of concern underscores the need to sustain efforts to monitor the emergence of new genotypes generated through recombination.
病毒重组可产生具有独特表型特征的新基因型,包括传播性和毒力。尽管β冠状病毒之间的重组能力已有充分记录,但SARS-CoV-2毒株之间重组的证据有限。通过识别主要决定SARS-CoV-2进化枝结构的突变,我们开发了一种轻量级方法来检测重组基因组。在查询的超过53.7万个基因组中,我们检测到1175个推定的重组体,它们包含来自不同进化枝的多个突变标记。进一步的系统发育分析以及在暴露地理区域中预测亲本进化枝的共同传播,进一步支持了这些检测到的病例中重组的可行性。对这些检测到的病例的分析未发现SARS-CoV-2基因组中存在重组热点的任何证据。尽管大多数重组基因型被检测到的次数有限,但现在至少有两种重组体广泛传播。还发现重组基因组包含与传播性增加和疫苗效力降低相关的关注替代突变,包括D614G、N501Y、E484K和L452R。调整检测来自不同亲本进化枝的重组体的不平等概率以及进化枝丰度的地理差异后,我们估计在美国和英国,循环病毒中最多5%是重组体。虽然对检测到的重组体的表型特征分析超出了我们的研究范围,但识别涉及关注替代突变的传播性重组体强调了持续监测通过重组产生的新基因型出现情况的必要性。