In the past 10 months, geneticists have studied the SARS-CoV-2 virus more intensively than any piece of RNA before. However, despite this in-depth investigation, a team of scientists from the American Museum of Natural History has discovered a hidden gene: a “gene within a gene”, which could explain why this virus is so infectious.
The new gene is called ORF3d and is technically known as an overlapping gene, since the nucleotide sequence of ORF3d is partially shared with another gene, that is, they are hidden in a nucleotide chain .
” Gene overlap may be one of the ways that coronaviruses have evolved to replicate efficiently , thwart host immunity, or pass on,” says Chase Nelson, postdoctoral researcher at Academia Sinica in Taiwan and visiting scientist at the Museum. American Journal of Natural History in the eLife journal that publishes the study.
“Knowing that there are overlapping genes and how they work can reveal new avenues for coronavirus control, for example through antiviral drugs.”
Is it a rare phenomenon?
No way. Viruses are quite prone to harboring overlapping genes, so it’s not exactly a discovery that puzzles scientists. What remains to be seen is whether ORF3d really represents a genomic hoax, but it is clearly a difficult thing to see. It is difficult to identify overlapping genes in genetic sequences because genomic scanning systems can often miss them when running through strings of genetic code because they are programmed to detect individual, non-overlapping genes.
In the virus at hand, SARS-CoV-2, this could constitute a serious blind spot. Scientists have been immersed in a race against the pandemic for months to understand it as much as possible in order to stop this coronavirus that has the world in suspense since the beginning of this year, and although some aspects of its genetic structure have been elucidated (including the fact that that it was not ‘made in a laboratory’), much remains to be elucidated.
What does the protein produced by ORF3d do?
It is unknown, but researchers have discovered that the new overlapping gene in SARS-CoV-2 has the potential to encode a protein that is longer than expected (a gene that is also present in a previously discovered pangolin coronavirus in Guangxi, China, suggesting that it may contain clues to the evolution of our current pandemic).
Independently, this gene elicits a strong antibody response in COVID-19 patients, indicating that the new gene protein is produced during infection in humans.
“We still don’t know what its function is or if it has any clinical significance,” Nelson clarifies. “However, we assume that, in contrast to the antibody response, this gene is relatively unlikely to be detected by a T-cell response. And perhaps that has something to do with how the gene arose.”
“In terms of genome size, SARS-CoV-2 and its relatives are among the longest RNA viruses out there. Therefore, they are perhaps more prone to ‘genomic tricks’ than other RNA viruses.” the expert concludes. Remember that RNA viruses (such as SARS-CoV-2) have a high mutation rate.
All of these discoveries are critical in the race to develop a vaccine and treatment for COVID-19. Hopefully soon we will discern what role this overlapping gene might have played in the emergence of the pandemic virus.
Referencia: Chase W Nelson et al, Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic, eLife (2020). DOI: 10.7554/eLife.59633
