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Understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is crucial for the development of vaccines and treatments. Since the pandemic began in December 2019, many studies have explored the origins of the virus and how it infects humans. In this way, scientists and doctors have an idea of how to fight the infection.
A team of researchers from Germany, Taiwan and the United States has identified and characterized a new hidden gene in SARS-CoV-2 that is also present in the Guangxi pangolin coronaviruses, although, curiously, closely absent in pangolin and bat coronaviruses. related.
What are overlapping genes?
The coronavirus pandemic raises urgent questions about the properties that allow viruses in animals to jump to humans. These types of diseases, called zoonoses, have affected human life for years, including the AH1N1 virus, bovine tuberculosis, glanders and bubonic plague, among others.
To better understand zoonotic diseases, it is essential to know more about viral genomes. One of the sources that is often overlooked is the evolution of new overlapping genes (OLG). In these genes, a single stretch of nucleotides encodes two different proteins in different reading frames.
SARS-CoV-2, in particular, has about 15 genes in total, and it is important to know more about them, including the overlapping genes.
“Gene overlap may be one of the ways that coronaviruses have evolved to replicate efficiently, thwart host immunity, or be transmitted,” Chase Nelson, postdoctoral researcher at Academia Sinica in Taiwan and visiting scientist at the Museum American Natural History, Explained.
“Knowing that there are overlapping genes and how they work can reveal new avenues for coronavirus control, for example through antiviral drugs,” he added.
Repertory of genes and evolutionary relationships of members of coronavirus species related to severe acute respiratory syndrome. Only genes downstream of ORF1ab are shown, starting with the Spike S gene. (A) Four types of genes and their relative positions in the SARS-CoV-2 Wuhan-Hu-1 genome (NCBI: NC_045512.2). Genes are colored by type: novel overlapping genes (OLG) (gold; ORF3d only); OLG preserved (burgundy); accessory (green); and structural (blue). Note that ORF3b has been truncated relative to the SARS-CoV genomes, while ORF8 remains intact (i.e., it has not split into ORF8a and ORF8b). (B) Genes with intact ORFs in each of the 21 coronavirus genomes related to severe acute respiratory syndrome. The positions of the genes are shown relative to each genome, that is, the homologous genes are not precisely aligned.
Identifying a new gene
In the current study, published in the journal eLife, The researchers identified ORF3d, a new gene overlaid in SARS-CoV2 that can potentially encode a protein that is longer than expected by chance. The researchers revealed that the gene is also present in previously discovered pangolin coronaviruses.
Additionally, the team found that the new gene has been shown to exhibit a strong antibody response in COVID-19 patients, indicating that the new gene’s protein is produced during human infection.
“We do not yet know its function or if it is of clinical importance. 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 came about, ”Nelson said.
Detecting overlapping genes is challenging, as most high-end and scientific computers are not designed to find them. However, these are common in coronaviruses since RNA viruses, such as SARS-CoV-2, have a high mutation rate. Therefore, viruses have developed a data compression system in which one letter of the genome can influence two or three different genes.
Implications of the study
The study of the genome of viruses, in particular SARS-CoV-2, can help us to better understand their characteristics and their evolution. This becomes crucial in the development of effective vaccines that can induce an adequate immune response to fight infection.
COVID-19 continues to spread rapidly around the world. In recent weeks, many countries have reported a second wave of infections. Countries in Europe, which had reopened their businesses and schools just a couple of months ago, are now seeing a resurgence of cases. However, these clusters of new infections have led to second closures in many countries, including Belgium, the United Kingdom, and Italy, which could have potential social, economic and psychological effects on the public.
The United States has the highest number of infections, reaching more than 10.39 million cases and 240,918 deaths. India and Brazil follow with more than 8.63 million and 5.69 million cases, respectively.
France reports more than 1.91 million cases, followed by Russia, Spain and Argentina, with more than 1.82 million, 1.41 million and 1.27 million cases, respectively.
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