Retrospect of the Two-Year Debate: What Fuels the Evolution of SARS-CoV-2: RNA Editing or Replication Error?

Mutation is one of the mechanisms of the evolutionary divergence of an organism. Under this global COVID-19 pandemic, the fast evolution of SARS-CoV-2 became one of the most worrying issues. Some researchers believed that the hosts’ RNA deamination systems (APOBECs and ADARs) are the major source of mutations and have driven the evolution of SARS-CoV-2. However, apart from RNA editing, the RDRP (RNA-dependent RNA polymerase)-mediated replication errors may also contribute to the mutation of SARS-CoV-2 (just like the single-nucleotide polymorphisms/variations in eukaryotes caused by DNA replication errors). Unfortunately, it is technically unable to distinguish RNA editing and replication errors (SNPs) in this RNA virus. Here comes a fundamental question: we indeed observed the fast evolution of SARS-CoV-2, but what exactly fuels its evolution: RNA editing or replication errors? This debate lasts for 2 years. In this piece, we will retrospect the 2-year debate on RNA editing versus SNPs.