Researchers from Taiwan, Germany and the United States have uncovered what they say is a new, previously unknown ‘overlapping gene’ hidden within the genetic code of SARS-CoV-2.
In a new research paper on the gene, which has been dubbed ‘ORF3d’, scientists led by Academia Sinica/American Museum of Natural History postdoctoral researcher Chase Nelson explain that the reason the gene lay undetected for so long was because it is carefully hidden from view, concealed within a string of nucleotides, and overlapping with the sequences of other genes.
“In terms of genome size, SARS-CoV-2 and its relatives are among the longest RNA viruses that exist,” Nelson explained in a press statement dedicated to the findings. “They are thus perhaps more prone to ‘genomic trickery’ than other RNA viruses,” he added.
ORF3d is an overlapping gene (OLG), that is, a gene within a gene. Because we are accustomed to assuming one gene per genome region, OLGs are often missed. Fig1A shows the last part of the SARS-CoV-2 genome, where the novel ORF3d is shown in gold and other OLGs in burgundy.
— Chase W. Nelson 倪誠志 (@chasewnelson) November 10, 2020
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“We don’t yet know its function or if there’s clinical significance,” Nelson continued, referring to potential ‘blind spots’ for man-made pharmaceutical treatments for combating the virus caused by the discovery. “We predict this gene is relatively unlikely to be detected by a T-cell response, in contrast to the antibody response,” the academic suggested, referring to the white blood cells found in the human body to help it fight off diseases.
Nelson and his colleagues expressed confidence that getting to know the coronavirus in more detail may help “reveal new avenues for coronavirus control, for example through antiviral drugs.”
Additionally, our analysis of natural selection in SARS-CoV-2 at three evolutionary levels—between-taxa, between-host, and within-host—reveals important patterns of change. For example, Fig5 suggests that another OLG, ORF3c, is highly functionally constrained in this virus.
— Chase W. Nelson 倪誠志 (@chasewnelson) November 10, 2020
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According to the researcher, it can’t be ruled out at this point that the ‘hidden gene’ may have come about as part of COVID-19’s evolution to replicate more efficiently, attack the immune system or aid in transmission. ORF3d is said to also be present in a previously found pangolin coronavirus, and to result in a strong antibody response in coronavirus-positive persons. The American Museum of Natural History specifies that the gene “has the potential to encode a protein that is longer than expected by chance alone.”
We also document evidence for the translation of ORF3d, provide a detailed annotation of the SARS-CoV-2 genome, & more. We hope that our paper will be a useful resource for investigations of this and other genes as we seek to better understand the origins of this pandemic.
— Chase W. Nelson 倪誠志 (@chasewnelson) November 10, 2020
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The discovery is potentially an important one, given that SARS-CoV-2 has a total of just 15 known genes. Overlapping genes are said to be relatively common, but can be notoriously difficult to detect because many of the computer-assisted tools scientists use to study viruses are not explicitly designed to find them.
Funding for the researchers’ investigation was provided by grants from Academia Sinica, which is a Taiwan-based research academy, the state government of Bavaria, Germany, a UK-based charity known as the National Philanthropic Trust (which receives funding from the Bill and Melinda Gates Foundation), the University of Wisconsin-Madison, and the US National Science Foundation (which also receives support from the tech billionaire).
The researchers' findings has been published in eLife, an open-access academic journal.
