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Researchers have discovered a mysterious gene in the genetic code of the SARS-CoV-2 coronavirus, a segment virtually hidden from view in the virus genome and largely overlooked until now.
The recently identified gene, called ORF3d – is an example of what is called an overlapping gene: a kind of ‘gene within a gene’ that is effectively hidden in a chain of nucleotides, due to the way it overlaps the encoded sequences of other genes.
“In terms of genome size, SARS-CoV-2 and its relatives are among the longest RNA viruses in existence,” explains bioinformatician Chase Nelson of the American Museum of Natural History.
“Therefore, they are perhaps more prone to ‘genomic tricks’ than other RNA viruses.”
Viruses are quite prone to harboring overlapping genes, so it’s not exactly a shocking discovery. Either ORF3d It really represents a genomic hoax that remains to be seen, but in any case, it is certainly difficult to see.
Overlapping genes are difficult to identify in genetic sequences, as genomic scanning systems can often miss them when running through strings of genetic code – programmed to detect individual genes, but do not necessarily see general instructions shared between the nucleotides of adjacent genes in a sequence.
In the context of viruses like SARS-CoV-2, that could become a serious blind spot. Scientists have been racing to understand as much as possible about this devastating virus since early this year, and while some aspects of its genetic makeup have been elucidated (including the strong consensus that it was not ‘made in a lab’), much remains that we just don’t know yet.
“The lack of overlapping genes puts us in danger of overlooking important aspects of viral biology,” says Nelson.
“Gene overlap may be one of the ways coronaviruses have evolved to replicate efficiently, thwart host immunity, or transmit themselves.”
As for ORF3dThere is still a lot to learn about why it is there, lurking in the genome and among other genes.
By scanning genomic databases, the researchers found that the gene had been identified before, but only in a variant of the coronavirus that affects pangolins (found in Guangxi, China).
It has also previously been wrongly classified as an unrelated gene, ORF3b – which is present in other coronaviruses, including SARS-CoV, but they are not actually the same.
“The two genes are not related and code for completely different proteins.” Nelson says. “This means that the knowledge about the SARS-CoV ORF3b should not apply to SARS-CoV-2 ORF3d. “
One thing we do know about the mystery gene, based on previous blood tests with human COVID-19 patients, is that ORF3d elicits a strong antibody response.
As to whether the T cells would also be activated, or for what other viral purposes the overlap ORF3d I could have, we’re still in the dark It could be relatively benign. It may not be so.
“We do not yet know its function or if there is clinical significance,” says Nelson.
“But we predict that this gene is relatively unlikely to be detected by a T-cell response, in contrast to the antibody response. And maybe that has something to do with how the gene might have arisen.”
One thing is for sure. In a virus that only has about 15 known genes, the discovery of another, much less an overlapping gene, is a significant advance. How significant, scientists will now try to find out.
Findings are reported in eLife.
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