Researchers have discovered a new “hidden” gene SARS-CoV-2 – The virus that causes COVID-19 – which may have contributed to its unique biology and epidemic potential. In viruses that contain only as many as 15 genes, knowing more about these and other overlapping genes – or “genes within genes” – can have a significant effect on how we deal with the virus. The new gene is described in today’s journal Elife.
“Overlapping genes could be an arsenal in which coronaviruses can evolve to effectively mimic, fail host immunity, or infect themselves,” said a postdoctoral researcher at Academia Sinika in Taiwan and a scientist scientist at the channel. . American Museum of Natural History. “Knowing that warping genes exist and how they work can reveal new ways to control coronavirus, for example through antiviral drugs.”
The research team identified ORF 3D, a new overlapping gene in SARS-Cavi-2 that is likely to encode longer proteins than expected by chance alone. They found that the gene was also present in the previously discovered pangolin coronavirus, possibly reflecting the frequent loss of the gene during the evolution of SARS-Cavi-2 and related viruses. In addition, ORF 3D has been identified independently and has been shown to show a strong antibody response in COVID-19 patients, indicating that a new gene protein is produced during human infection.
“We don’t know if it’s still of medical importance,” Nelson said. “But we hypothesize that unlike the antibody response, it is not possible for this gene to be detected by the T-cell response. And maybe it has something to do with how the gene was able to be produced. “
At first glance, genes look like written language that is made up of a string of letters (in RNA Viruses, nucleotides A, U, G and C) that deliver information. But while the units of language (words) are independent and non-la overlapping, genes can be overlapping and multifunctional, with secretly encoded information depending on where you start “reading”. Overlapping genes are difficult to find, and most scientific computer programs are not designed to detect them. However, they are common in viruses. This is partly because the RNA Viruses have a high mutation rate, so they keep their gene counts low to prevent a large number of mutations. As a result, the virus has developed a type of data compression system in which a single character in its genome can contribute two or three different genes.
“Missing overlapping genes make us overlook important aspects of viral biology.” “In terms of genome size, SARS-Covy-2 and its relatives are one of the longest surviving RNA viruses. This way they are more likely to have a ‘genomic trick’ than other RNA viruses. ”
Prior to the epidemic, while working at the museum as a Gerstner scholar in bioinformatics and computational biology, Nelson developed a computer program that screens genomes for patterns of genetic mutations that are unique to overlapping genes. For this study, Nelson worked with collaborators from institutions including the University of Munich and the Technical University. University of California, Berkeley, To apply this software and other methods to the new sequence data data available for SARS-CoV-2. The group hopes that other scientists will examine the gene in the lab to determine its function and possibly determine what role it may have played in the emergence of the epidemic virus.
References: Chase W. Nelson, Zachary Arden, Tony L. Goldberg, Chen Meng, Chen-Hao Kuo, Christina Ludwig, Sergios-Orestes Kolokotronis, and Zinzu Wei 2020, Elife.
DOI: 10.7554 / Elife.5593
The work was funded by Academia Sinica, the Bavarian state government, and 12 national philanthropic trusts, the U.S. Granted by the National Science Foundation (Grants Nos. 1755370 and 1758800, and the University of Wisconsin-Madison).
