Ongoing Adaptive Evolution and Globalization of Sars-Cov-2

Rochman, Nash D.; Wolf, Yuri I.; Faure, Guilhem; Zhang, Feng; Koonin, Eugene V.

Unprecedented sequencing efforts have, as of October 2020, produced over 100,000 genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the ongoing COVID-19 crisis. Understanding the trends in SARS-CoV-2 evolution is paramount to control the pandemic. Although this extensive data availability quickly facilitated the development of vaccine candidates(1), major challenges in the analysis of this enormous dataset persist, limiting the ability of public health officials to translate science into policy. Having evolved over a short period of time, the SARS-CoV-2 isolates show low diversity, necessitating analysis of trees built from genome-scale data. Here we provide a complete ancestral genome reconstruction for SARS-CoV-2 leveraging Fitch Traceback(2). We show that the ongoing evolution of SARS-CoV-2 over the course of the pandemic is characterized primarily by purifying selection. However, a small set of sites, including the extensively studied spike 614(3), harbor mutations which recurred on multiple, independent occasions, indicative of positive selection. These mutations form a strongly connected network of apparent epistatic interactions. The phylogenetic tree of SARS-CoV-2 consists of 7 major clades which show distinct global and temporal dynamics. Periods of regional diversification of SARS-CoV-2 are short and, despite dramatically reduced travel(4), globalization of the virus is apparent.