Emergence and widespread circulation of a recombinant SARS-CoV-2 lineage in North America

Abstract

Genetic recombination is an important driving force of coronavirus evolution. While some degree of virus recombination has been reported during the COVID-19 pandemic, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation and been observed only in restricted areas. Prompted by reports of unusual genetic similarities among several Pango lineages detected mainly in North and Central America, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages (B.1.627, B.1.628, B.1.631 and B.1.634) in order to investigate the possibility of virus recombination among them. Two of these lineages, B.1.628 and B.1.631, are split into two distinct clusters (here named major and minor). Our phylogenetic and recombination analyses of these lineages find well-supported phylogenetic differences between the Orf1ab region and the rest of the genome (S protein and remaining reading frames). The lineages also contain several deletions in the NSP6, Orf3a and S proteins that can augment reconstruction of reliable evolutionary histories. By reconciling the deletions and phylogenetic data, we conclude that the B.1.628 major cluster originated from a recombination event between a B.1.631 major virus and a lineage B.1.634 virus. This scenario inferred from genetic data is supported by the spatial and temporal distribution of the three lineages, which all co-circulated in the USA and Mexico during 2021, suggesting this region is where the recombination event took place. We therefore support the designation of the B.1.628 major cluster as recombinant lineage XB in the Pango nomenclature. The widespread circulation of lineage XB across multiple countries over a longer timespan than the previously designated recombinant XA lineage raises important questions regarding the role and potential effects of recombination on the evolution of SARS-CoV-2 during the ongoing COVID-19 pandemic.

Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic

“…The level, scale and consequences of recombination during the pandemic are unclear; one earlier study of phylogenetic inconsistency found no clear signals of recombination 93 , whereas a more recent analysis of UK sequence data discovered at least four groups of natural recombinants of B.1.1.7 and other parental lineages 94 . The increasing co-circulation in 2021 of genetically diverse viruses increases the likelihood that further SARS-CoV-2 recombinants will be detected 95 .…”

Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages

“…New reports supporting evidence of recombination events have started emerging, including evidence of recombination between B.1.1.7 and B.1.177 lineages and evidence supporting the recombining origins of lineage B.1.628 ( 51 ). More recently, a group reported the first case of an intra-host recombination event during a co-infection with Delta and Gamma of the sample in the study ( 52 ). This is the first reporting of a recombination event during co-infection of an individual.…”

Emergence of Within-Host SARS-CoV-2 Recombinant Genome After Coinfection by Gamma and Delta Variants: A Case Report

“…Recent studies reported the detection of SARS-CoV-2 recombinant lineages circulating at a low frequency ( 11 , 12 , 18 – 21 ). Nevertheless, these studies were restricted to detecting the inter-host dissemination of genomes post-recombination events, which could be biased by spurious mutations generated due to library preparation, laboratory contamination, and unavailability of raw sequenced data.…”

“…Indeed, this phenomenon occurs at a relatively high frequency among betacoronaviruses ( 8 – 10 ). In SARS-CoV-2, signals of ongoing recombination were observed in a few sequences deposited in GISAID and circulating in North America ( 11 , 12 ). Both studies showed evidence of recombination between non-variants of concern.…”