Abstract
Unprecedented sequencing efforts have, as of October 2020, produced nearly 200,000 genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. Understanding the trends in SARS-CoV-2 evolution is paramount to control the pandemic, but analysis of this enormous dataset is a major challenge. We show that the ongoing evolution of SARS-CoV-2 over the course of the pandemic is characterized primarily by purifying selection but a small set of sites, including spike 614 and nucleocapsid 203-204 appear to evolve under positive selection. In addition to the substitutions in the spike protein, multiple substitutions in the nucleocapsid protein appear to be important for SARS-CoV-2 adaptation to the human host. The positively selected mutations form a strongly connected network of apparent epistatic interactions and are signatures of major partitions in the SARS-CoV-2 phylogeny. These partitions show distinct spatial and temporal dynamics, with both globalization and diversification trends being apparent.
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