In the last 10 months, geneticists have studied SARS-CoV-2 more intensely than any stretch of RNA before. Consequently, we might not expect to find a new gene at this late stage, particularly since it only has 15. Nevertheless, that is what is being reported, with scientists describing the discovery as a “gene within a gene”.
The new gene is named ORF3d and reported in the journal eLife. Technically known as an overlapping gene, ORF3d's nucleotide sequence is partially shared with another gene. It's like the puzzles where the last letters of one word and the first of another are the same, but only written once to trick the reader.
How important ORF3d's role is in making the virus so easily transmitted and deadly is not yet known, let alone whether it could provide a point of weakness we could use to attack the invader.
"Overlapping genes may be one of an arsenal of ways in which coronaviruses have evolved to replicate efficiently, thwart host immunity, or get themselves transmitted," said Dr Chase Nelson of Academia Sinica, Taiwan, in a statement. “Knowing that overlapping genes exist and how they function may reveal new avenue for coronavirus control, for example through antiviral drugs.”
Genes are sequences of nucleotides that encode to produce a protein. Nelson and co-authors don't yet know what the protein made by ORF3d does, but have found it produces a strong antibody response in people recovering from Covid-19. This indicates the protein is produced during the course of the disease leading the body to produce antibodies to fight it.
"We don't yet know its function or if there's clinical significance," Nelson said. "But we predict this gene is relatively unlikely to be detected by a T-cell response, in contrast to the antibody response.”
Computer programs created to speed up the process of finding new genes are usually not suited to finding overlapping sequences, which is why this one was missed until now. Nevertheless, many viruses have them, particularly RNA viruses like SARS-CoV-2 where the mutation rate is high. Even before Covid-19 appeared Nelson thought overlapping genes might be understudied and created a program to look for signs of their presence.
Nelson noted SARS-CoV-2 is from a family that contains some of the longest RNA viruses we have found and thinks this may indicate they have some “genomic trickery” up their sleeves. Applying his program to SARS-CoV-2, Nelson found ORF3d, which had previously been confused with ORF3b, a gene found in the original SARS virus.
Intriguingly ORF3d is also found in previously discovered pangolin coronaviruses from Guangxi, China, suggesting it may hold clues to the evolution of our current pandemic. However, it does not appear in more closely related pangolin or bat coronaviruses.