Researchers have discovered a mysterious gene in the genetic code of the SARS-CoV-2 coronavirus, a segment almost hidden from view in the virus's genome and still overlooked.
The newly identified gene – ORF3d – is an example of what is called an overlapping gene: a kind of 'gene within a gene' that effectively hides itself in the chain of nucleotides due to the fact that 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 bioinformatist Chase Nelson of the American Museum of Natural History.
“Thus, they are more susceptible to 'genomic trickery' than other RNA viruses.”
In fact, viruses are very prone to overlapping genes, so this is not exactly a surprising discovery. It remains to be seen if ORF3d is indeed a genomic hoax, but it is definitely difficult to see anyway.
Overlapping genes are difficult to identify in genetic sequences because genomic scanning systems can often skip them when scanning lines of genetic code: they are programmed to select individual genes, but do not necessarily see overarching instructions common to the nucleotides of neighboring genes in the sequence.
Electron micrograph of SARS-CoV-2 virus particles. (NIAID).
In the context of viruses such as SARS-CoV-2, this can create a serious blind spot. Scientists have been striving to understand as much as possible about this devastating virus since the beginning of this year, and although some aspects of its genetic structure have been elucidated (including the firm belief that it was not 'created in the laboratory'), there is just a lot we just don't know yet. .
“Overlapping genes may be one of the arsenal of ways coronaviruses have evolved to replicate efficiently, undermine host immunity, or transmit themselves.”
As for ORF3d, there is still a lot to be learned about why it exists, hides in the genome, and overlaps other genes.
One thing we know for sure about the mysterious gene, based on previous blood tests from COVID-19 patients, is that ORF3d does trigger a strong antibody response.
“We don't yet know its function and clinical significance,” says Nelson.
“But we predict that this gene is relatively unlikely to be detected by a T cell response, as opposed to an antibody response. And perhaps it has something to do with how the gene was able to arise. '
One thing is certain. For a virus that has only about 15 known genes, the discovery of yet another, let alone an overlapping gene, is a significant advance. How important, scientists will now try to find out.
The results are reported to eLife.
