The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spawned interest in the role of recombination in the evolution of this new virus as well as other human coronaviruses (hCoV). Recombination is the natural or artificial rearrangement of genetic material in living organisms or viruses. Scientists have previously observed recombination in many RNA viruses. Recombination is found to occur at a higher frequency in positive-sense RNA viruses, including SARS-CoV-2 and other medically significant coronaviruses.
Recombination in RNA viruses has been linked to changes in host range, virulence, and host response. Identifying the presence of recombination and predicting the risk of recombination during the SARS-CoV-2 pandemic is critical for various reasons. This is because circulating recombinants of the virus may complicate molecular diagnostics and help the virus escape naturally acquired immunity. This has been observed in the norovirus genus that has caused pandemics owing to the rapid emergence of new genotypes emerging from the recombination of structural genes. Such recombination events may have serious implications for SARS-CoV-2, especially if the recombinants can escape both natural and vaccine-induced immunity.
Genomic epidemiology is a powerful public health tool for SARS-CoV-2, and neglecting the recombinant data may result in incorrect epidemiological inference due to possible phylogenetic incongruence.
A comprehensive recombination analysis across medically important human coronaviruses
Recently, a team of researchers from the US performed a comprehensive recombination analysis across all medically relevant human coronaviruses, including 158,118 public seasonal hCoV, SARS-CoV-1, SARS-CoV-2, and MERS-CoV genome sequences with the help of the RDP4 software. They aimed at identifying the current and future risks of the emergence of recombinants of SARS-CoV-2. The study is published on the preprint server, bioRxiv*.
The researchers found moderate evidence for SARS-CoV-2 recombination in the first year of the pandemic. Concerning other hCoV species, they observed that recombination has a preference for structural genes and is relatively frequent in most relevant hCoVs over a comparatively short evolution timescale. According to the authors, these results are timely going by the recent announcement of a recombinant SARS-CoV-2 strain and the increasing focus on the functional implications of antigenic evolution in seasonal coronaviruses.
“In other hCoV species, we note that recombination has a predilection for structural genes and is relatively frequent in most medically significant hCoV over a relatively short evolution timescale.”
Results indicate relatively low viral diversity in the first year of the pandemic
The researchers noted 8 instances of recombination in over 100,000 SARS-CoV-2 genomes, and 2 of them involve the spike gene. However, the RDP4 software flagged all these instances of recombination as possibly driven by other processes though they were supported by 3 or more recombination detection methods. This may indicate the relatively lower viral diversity in the first year of the COVID-19 pandemic. Similarly, there was no high-confidence recombination signal in SARS-CoV-1, which is a virus with limited temporal distribution.
“Our endemic coronavirus analyses also highlighted that recombination affected the estimated temporal structure of coronavirus sequence datasets.”
Findings highlight the significance of genomic surveillance in detecting SARS-CoV-2 recombination
Recombination was comparatively frequent in MERS-CoV and seasonal coronavirus datasets, including recombinants that are fit enough for onward transmission. Moreover, the analyses showed that 3 of the coronaviruses - MERS, OC43, and NL63 - had breakpoint predilection for structural genes. Among the MERS-CoV, 229E, OC43, NL63 and HKU1 datasets, they noted 7, 1, 9, 14, and 1 high-confidence recombination events, respectively.
“We show that recombination was relatively frequent in seasonal coronavirus and MERS-CoV datasets comprising a longer period of sampling, including recombinants sufficiently fit for onward transmission.”
Bayesian time-scaled analyses on recombinant-free data showed the diversity of seasonal CoVs emerged in the last 70 years, with HCoV-229E displaying continuous lineage replacements. According to the authors, these findings highlight the importance of genomic-based surveillance in the detection of SARS-CoV-2 recombination, especially if recombination may result in immune evasion.
“Ongoing genomic-based COVID-19 surveillance has recently been highlighted as a critical public health tool to detect novel SARSCoV-2 variants, such as the B.1.1.7, B.1.351, and P.1 variants.”
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- A comparative recombination analysis of human coronaviruses and implications for the SARS-CoV-2 pandemic, Simon Pollett, Matthew A Conte, Mark A Sanborn, Richard G Jarman, Grace M Lidl, Kayvon Modjarrad, Irina Maljkovic Berry, bioRxiv, 2021.03.07.434287; doi: https://doi.org/10.1101/2021.03.07.434287,