Positive Selection of ORF1ab, ORF3a, and ORF8 Genes Drives the Early Evolutionary Trends of SARS-CoV-2 During the 2020 COVID-19 Pandemic

Authors: VELAZQUEZ-SALINAS, LAURO - University Of Kansas; ZARATE, SELENE - New Mexico State University; EBERL, SAMANTHA - Central Connecticut State University; Gladue, Douglas; NOVELLA, ISABEL - University Of Toledo; Borca, Manuel

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/28/2020
Publication Date: 10/23/2020
Citation: Velazquez-Salinas, L., Zarate, S., Eberl, S., Gladue, D.P., Novella, I., Borca, M.V. 2020. Positive selection of ORF1ab, ORF3a, and ORF8 genes drives the early evolutionary trends of SARS-CoV-2 during the 2020 COVID-19 pandemic. Frontiers in Microbiology. https://doi.org/10.3389/fmicb.2020.550674.
DOI: https://doi.org/10.3389/fmicb.2020.550674

Interpretive Summary: SARS-CoV-2 the virus responsible for the pandemic of COVID-19, has caused one of the most significant public health events of this century. Currently, there is little knowledge about some key aspects in the biology of this virus necessary to establish proper control measures. In this context, determining the evolutionary pattern of COVID-19 is important to understand the generation of new viral variants during the pandemic. This information might also help to explain differences observed in clinical outcomes among people around the world and predict the success of specific vaccines used to control this pandemic. For these reasons, we focused on understanding the early evolutionary patterns of SARS-CoV-2 during the beginning of the pandemic. Using different bioinformatic approaches, we identified potential viral variants that arose early during the pandemic. Our results showed that at least three different groups of variants evolved early during the pandemic. We also identified potential critical sites in the genome of SARS-COV-2 for evolutionary studies, as well as different evolutionary mechanisms involved in the evolution of variants. Collectively, our results highlight the potential of SARS-CoV-2 to rapidly evolve during the pandemic and suggest that multiple variants of this virus with different levels of virulence may be circulating in the world.

Technical Abstract: In this study, we analyzed full-length SARS-CoV-2 genomes from multiple countries to determine early trends in the evolutionary dynamics of the novel COVID-19 pandemic. Results indicated SARS-CoV-2 evolved early into at least three phylogenetic groups, characterized by positive selection at specific residues of the accessory proteins ORF3a and ORF8. Also, we are reporting potential relevant sites under positive selection at specific sites of non-structural proteins nsp6 and helicase. Our analysis of co-evolution showed evidence of epistatic interactions among sites in the genome that may be important in the generation of variants adapted to humans. These observations might impact not only public health but also suggest that more studies are needed to understand the genetic mechanisms that may affect the development of therapeutic and preventive tools, like antivirals and vaccines. Collectively, our results highlight the identification of ongoing selection even in a scenario of conserved sequences collected over the first 3 months of this pandemic.