Investigating the evolutionary origins of the first three SARS-CoV-2 variants of concern

The emergence of Variants Concern (VOCs) SARS-CoV-2 with increased transmissibility, immune evasion properties, and virulence poses a great challenge to public health. Despite unprecedented efforts increase genomic surveillance, fundamental facts about the evolutionary origins VOCs remain largely unknown. One major uncertainty is whether evolved during transmission chains many acute infections or long-term within single individuals. We test consistency these two possible paths observed dynamics, focusing on clustered first three VOCs, Alpha, Beta, Gamma, in late 2020, following period relative stasis. consider range fitness landscapes, which VOC phenotypes could be result mutations, multiple mutations that each contribute additively increasing viral fitness, epistatic interactions among do not individually fitness—a “fitness plateau”. Our results suggest timing dynamics emergence, together number lineages, are best agreement phenotype requiring having individuals infections.