A team of researchers led by bioinformatics scientist Chase Nelson of the American Museum of Natural History has discovered a mysterious new hidden gene in the virus genome responsible for the pandemic of Covid-19. The new gene, identified as ORF3d, had thus far managed to escape the scrutiny of scientists, who had overlooked it.
In an article just published in the magazine eLife, it is explained that it is an example of what is known as an “overlapping gene”, a kind of “gene within a gene” that remains hidden in a nucleotide chain thanks to the way in which it overlaps the encoded sequences from other genes.
“In terms of genome size,” Nelson explains, “the SARS-CoV-2 and its relatives are among the longest RNA viruses in existence. Therefore, they are perhaps more prone to ‘genomic tricks’ than other similar viruses.’
According to the researcher, viruses are quite prone to harboring overlapping genes, which are difficult to identify since genetic scanning systems, programmed to identify individual genes, often miss them.
It remains to be determined what the specific function of this new gene is, but the researchers believe that the mere fact of not having detected it so far is a ‘serious blind spot»To our knowledge of the virus. Scientists have been studying this coronavirus since the beginning of the year at a frantic pace to try to mitigate its devastating effects. And although important aspects of the genetic makeup of SARS-CoV-2 have already been elucidated, much is still unknown.
“Not detecting overlapping genes,” says Nelson, “puts us at risk of missing important aspects of the biology of the virus. Gene overlap may be one of the ways coronaviruses have evolved to replicate efficiently, bypass host immunity, or be transmitted.
In the case of ORF3d, the researcher maintains, it is still necessary to understand why it is there, lurking, hidden among other genes. By scanning existing databases, Nelson and his colleagues found that the gene had already been identified before, although only in a variant of the coronavirus that affects pangolins, in China.
Previously, it had also been misclassified as an unrelated gene, called ORF3b, which is present in other coronaviruses as well, but Nelson believes this is not the same. “The two genes – he explains – are not related and code for completely different proteins. This means that the knowledge about SARS-CoV-2 ORF3b should not be applied to SARS-CoV-2 ORF3d ”.
One thing that is known about the mysterious gene (thanks to previous blood tests of Covid-19 patients) is that ORF3d elicits a strong antibody response. As for whether the gene contributes to the activation of our body’s T cells, or whether it serves other obscure purposes for the virus, we still don’t know anything. Its specific action could be totally harmless, but also the opposite.
In Nelson’s words, ‘still we do not know its function, or if it is of clinical significance. But we predict that this gene is relatively unlikely to be detected by a T-cell response, in contrast to the antibody response. Maybe this has something to do with its origin.
For Nelson, however, one thing is for sure. In a virus that only has 15 known genes, the finding of another, and even more if it is an overlapping gene, is a very significant advance. To what extent, is something that scientists will now have to discover.