Coordinated evolution at amino acid sites of SARS-CoV-2 spike

• DOI: 10.7554/elife.82516
• Publication Date: 2023-02-02T15:08:21Z
• Authors: Alexey Dmitrievic...; Gennady Fedonin; Anfisa Popova; Daria Bykova; Georgii Bazykin
• Keywords: Epistasis; Lineage (genetic); Molecular evolution

SARS-CoV-2 has adapted in a stepwise manner, with multiple beneficial mutations accumulating rapid succession at origins of VOCs, and the reasons for this are unclear. Here, we searched coordinated evolution amino acid sites spike protein SARS-CoV-2. Specifically, concordantly evolving site pairs (CSPs) which changes one were rapidly followed by other same lineage. We detected 46 formed 45 CSP. Sites CSP closer to each structure than random pairs, indicating that concordant functional basis. Notably, carrying lineage defining four VOCs circulated before May 2021 enriched CSPs. For Alpha VOC, enrichment is even if sequences removed from analysis, VOC origin could have been facilitated positive epistasis. Additionally, nine discordantly where unexpectedly rarely occurred on background specific allele another site, example wild-type D 614 (four pairs) or derived Y 501 (three pairs). Our findings hint epistasis between delayed assembly advantageous combinations comprising least some VOCs.