Explained | To err is viral: Why do most deadly viruses contain RNA?

While most organisms prefer DNA to store genetic information due to its proofreading function, many disease-causing viruses have benefited from having RNA because of the hit-or-miss nature of RNA polymerase.

In March 1953, James Watson, the co-discoverer of the structure of DNA, received a note from Harriett Ephrussi-Taylor, a friend from the National Centre for Scientific Research in France. The note, titled “Top Secret”, contained news of a potential discovery that had enormous implications for molecular biology, virology, and immunology. 

The note read, “Burnet swears, from work in his lab, that flu virus has principally, possibly exclusively, RNA. Suspects same for Polioviruses.”

Most organisms prefer DNA over RNA, its chemical cousin, to store genetic information. As life evolved from single-celled organisms to increasingly complex forms, the amount of genetic data that had to be transferred to subsequent generations became correspondingly higher. So organisms needed to make sure that the mechanism for copying the genetic material was that much more robust.

In particular, organisms needed the ability to correct any inadvertent errors in the copying mechanism. The enzymes responsible for copying DNA, collectively known as DNA polymerases, possess this error-correction property, known in technical parlance as ‘proofreading’. This proofreading ability allowed the total DNA of higher organisms, known as the genome, to be longer and more complex.

On the other hand, the RNA counterparts to DNA polymerases, known as RNA polymerases, do not possess the ability to proofread. As a result, when RNA is the genetic material, the genomes typically tend to be shorter. Longer genomes would contain proportionately higher mistakes, and such genomes would be eliminated by natural selection.

Coronaviruses beautifully illustrate this point since their genomes are typically three- or four-times the size of those of other RNA viruses. They can afford the longer genomes due to the presence of a unique protein, in addition to the RNA polymerase, that performs the proofreading function.

RNA polymerases are also capable of recombination, a process that allows them to stitch together multiple pieces of different viral RNAs. This way, if one viral RNA contains a mutation at location X and another contains a mutation at location Y, recombination can create a virus containing both X and Y by sewing the two regions of the viral RNA containing those mutations. This is how, for example, the XBB variant of SARS-CoV-2 is the product of the BA.2.10.1.1 and BA.2.75.3.1.1.1 variants.