Coronavirus genomics and bioinformatics analysis

National Library Of Medicine

Investigators

Linked publications & trials

Abstract

Recombination between coronaviruses plays an important role in coronavirus evolution and can alter host range, pathogenicity, and transmission pattern. Novel coronaviruses, including SARS-CoV-2, SARS-CoV, and MERS-CoV, often originate from recombination events. In the midst of the current COVID-19 pandemic, it is of great importance to understand the patterns of recombination in coronaviruses. Recombination in coronaviruses occurs when the RNA-dependent RNA polymerase (RdRp) switches the templates during cRNA synthesis, a process called template switching. Coronavirus transcription also involves template switching and TRS-B is a signal for RdRP to switch templates. It has been hypothesized that recombination events are more likely to occur at or near TRS-B sites. In this project we investigated the relationship between genome recombination in coronaviruses and template switching at TRS-B sites. We developed a tool called SuPER to systematically identify TRS sites within coronavirus genomes, by which we systematically identified TRS sites in all available coronavirus genomes, and found that the TRS-L CS and secondary structure is conserved within genera but differs between genera. We analyzed available Coronaviridae genomes and found that recent inter-subgenus recombination is rare. We then used RDP4 to detect putative recombination events and discovered that recombination events are extensive within subgenera. We also detected that several recombination events occurred between the ancestors of SARS and SARS-CoV-2, implying the potential for recombination between SARS and SARS-CoV-2. We further characterized the recombination loci and showed that recombination hotspots are more frequently co-located with TRS-B sites than expected. Results from this project helps to predict which coronaviruses are most likely to recombine with SARS-CoV-2, which can inform policy decisions going forward. Additionally, if attenuated virus vaccines are used in the current COVID-19 pandemic or for future coronavirus outbreaks, understanding patterns of recombination will inform the strategies used to prevent reversion to a virulent phenotype. Overall, this work helps to inform and predict coronavirus genome recombination and could provide insights into the prevention and prediction of future coronavirus outbreaks. Our results including the SuPER tool and the analysis have been reported in a manuscript and published.