New ‘hidden’ gene identified in Covid-19 virus

Researchers have identified a new “hidden” gene in SARS-CoV-2, the virus responsible of COVID-19, which may have contributed to its unique biology and pandemic potential.

In a virus that only has about 15 genes in total, knowing more about this and other overlapping genes – or “genes within genes” – could have a significant impact on how we fight the virus.

“Gene overlap may be one of an arsenal of ways coronaviruses have evolved to replicate efficiently, counter host immunity, or be transmitted,” said lead author Chase Nelson, postdoctoral researcher at the Sinica Academy of Taiwan and visiting scientist at the American Museum of Natural History.

“Knowing that overlapping genes exist and how they work can reveal new avenues for coronavirus control, for example through antiviral drugs “.

The research team identified ORF3d, a new overlapping gene in SARS-CoV-2 that has the potential to encode a protein that is longer than expected just by chance, according to the study published in the journal eLife.

They found that this gene is also present in a previously discovered pangolin coronavirus, possibly reflecting the repeated loss or gain of this gene during the evolution of SARS-CoV-2 and related viruses.

Furthermore, ORF3d has been independently identified and has been shown to elicit a strong antibody response in patients with Covid-19, demonstrating that the new gene protein is produced during human infection.

“We don’t yet know its function or if there is any clinical significance,” Nelson said.

“But we anticipate that it is relatively unlikely that this gene will be detected by a T cell response, as opposed to the antibody response. And perhaps this has something to do with how the gene was able to arise.”

At first glance, genes may seem like a written language as they are made of strings of letters (in RNA viruses, the nucleotides A, U, G and C) that transmit information.

But while the units of language (words) are discrete and do not overlap, genes can be overlapping and multifunctional, with information coded cryptically depending on where you start “reading”.

Overlapping genes are hard to spot, and most scientific computer programs aren’t designed to find them. However, they are common in viruses.

This is partly due to the fact that RNA viruses have a high mutation rate, so they tend to keep the number of genes low to prevent large numbers of mutations.

As a result, viruses have developed a kind of data compression system in which a letter in its genome can contribute to two or even three different genes.

“The lack of overlapping genes puts us in danger of neglecting important aspects of viral biology,” Nelson said.

“In terms of genome size, SARS-CoV-2 and its relatives are among the longest RNA viruses that exist. They are therefore perhaps more prone to ‘genomic deception’ than other RNA viruses.”