Post by Nadica (She/Her) on Jul 21, 2024 9:07:36 GMT
Early evolution of the BA.2.86 variant sheds light on the origins of highly divergent SARS-CoV-2 lineages - Preprint posted July 19, 2024
Abstract
Throughout the evolutionary history of SARS-CoV-2, divergent variants with an unusually high number of novel mutations have repeatedly emerged and displaced other lineages in co-circulation. The latest example is the BA.2.86 Variant Of Interest (VOI), which rapidly outcompeted all other lineages following its detection in late July 2023. Descending sublineages dominated globally by July 2024, at the time of writing this study. The mechanisms by which highly-divergent viral lineages tend to emerge remain unclear, with the most strongly supported hypothesis being the acquisition of multiple mutations through accelerated evolution in chronically infected individuals, with spread back into the community facilitated by prolonged shedding. We used BA.2.86 as a case study to investigate the evolutionary process behind the emergence of a highly divergent SARS-CoV-2 variant. Through fine-scale evolutionary analyses applied to four independently subsampled datasets, we identify over 100 genomes representing evolutionary intermediates occupying the branch in the phylogenetic tree leading to the BA.2.86*/JN.1* clade. Additionally, we detected more than 2,600 hybrid genomes across the evolutionary history of the Omicron-descending BA.2* sub-lineages, displaying a sequential acquisition of BA.2.86 lineage-defining mutation constellations through time. We observe that hybrid strains circulated up to 19 months prior to BA.2.86, denoting cryptic circulation in various countries, with further evidence of early transmission chains. We also found signals of recombination between pre-existing parental lineages, suggesting that this process contributed to the emergence of BA.2.86. Our results suggest that the BA.2.86 lineage emerged sequentially through a complex evolutionary process, rather than via accelerated evolution associated with a single emergence event.
Abstract
Throughout the evolutionary history of SARS-CoV-2, divergent variants with an unusually high number of novel mutations have repeatedly emerged and displaced other lineages in co-circulation. The latest example is the BA.2.86 Variant Of Interest (VOI), which rapidly outcompeted all other lineages following its detection in late July 2023. Descending sublineages dominated globally by July 2024, at the time of writing this study. The mechanisms by which highly-divergent viral lineages tend to emerge remain unclear, with the most strongly supported hypothesis being the acquisition of multiple mutations through accelerated evolution in chronically infected individuals, with spread back into the community facilitated by prolonged shedding. We used BA.2.86 as a case study to investigate the evolutionary process behind the emergence of a highly divergent SARS-CoV-2 variant. Through fine-scale evolutionary analyses applied to four independently subsampled datasets, we identify over 100 genomes representing evolutionary intermediates occupying the branch in the phylogenetic tree leading to the BA.2.86*/JN.1* clade. Additionally, we detected more than 2,600 hybrid genomes across the evolutionary history of the Omicron-descending BA.2* sub-lineages, displaying a sequential acquisition of BA.2.86 lineage-defining mutation constellations through time. We observe that hybrid strains circulated up to 19 months prior to BA.2.86, denoting cryptic circulation in various countries, with further evidence of early transmission chains. We also found signals of recombination between pre-existing parental lineages, suggesting that this process contributed to the emergence of BA.2.86. Our results suggest that the BA.2.86 lineage emerged sequentially through a complex evolutionary process, rather than via accelerated evolution associated with a single emergence event.