Aakancha Shaw, St. Xavier’s College, Kolkata
Just a few months after the Covid-19 pandemic began, scientists were able to sequence the full genome of the SARS-CoV-2virus that had caused the infection. Most of its genes were already known then but the full complement of protein-coding genes remained unresolved. After performing an extensive comparative study, researchers have developed the most accurate and complete gene annotation of the SARS-CoV-2 virus. They also confirmed the presence of several protein-coding genes and also came across a few others that were thought to be genes but they were found to not code for any proteins. The scientists used a comparative genomics approach to discover and know about the functional protein-coding content of the genes. About 2,000 mutations have been seen in different SARS-CoV-2 isolates since it began infecting humans, or rather since the pandemic. These required research to observe the changing the virus’s ability to evade the immune system and become more infectious.
Comparative genomics involves identifying several regions that are known to encode protein-coding genes. This is done based on their similarity to protein-coding genes found in similar related viruses. The researchers compared the genome of similar viruses to understand which part of the virus, SARS-CoV-2 contained genes. The virus is known to belong to a subgenus of viruses commonly known as Sarbecovirus. These are known to mostly infect bats. The researchers performed their comparative analysis by comparing SARS-CoV-2, SARS-CoV (caused the 2003 SARS outbreak), and other 42 strains of bat sarbecoviruses. The method is based on analyzing whether certain DNA or RNA bases are conserved between species, and thereby comparing their patterns of evolution over time.
Alongside the five protein-coding genes that common in all viruses, SARS-CoV-2 also shows the presence of six other protein-coding genes. It was observed that the region encoding a gene called ORF3a also encodes an additional gene- ORF3c. It consists of RNA bases that overlap with ORF3a but it occurs in a different reading frame. This type of “gene-within-a-gene” is quite rarely seen in large genomes but is commonly seen in many viruses, whose genomes are under selective pressure to stay compact. The role of this new gene is not known yet. Five other regions that were proposed as possible genes were shown to not encode any functional proteins. And the scientists ruled out the possibility of such genes that are yet to be discovered.
Again, the researchers studied all the 2000 mutations that have arisen in the SARS-CoV-2 since the pandemic. For each gene, they compared how much that specific gene has evolved in the past vs how much it has evolved since the start of the pandemic. They identified a region of the nucleocapsid protein that surrounded the viral genetic material. It had more mutations than was expected of it by observing its history. The most mutation-prone region in the entire genome of the virus lies in the middle of this nucleocapsid protein.
It was discovered that the variants that lack mutations in that region got recognized by the human immune system while those variants that randomly mutate in that region were able to evade the immune system and survive for a longer period. The evolutionary context of these mutant variants needs to be studied to understand how the current pandemic fits in the history of virology.
Also read:DRDO’s “2-DG” Anti-Covid Drug has been finally launched
References: Jungreis, I., Sealfon, R. & Kellis, M. SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes. Nat Commun 12, 2642 (2021). https://doi.org/10.1038/s41467-021-22905-7
- The Corrosion Prediction from the Corrosion Product Performance
- Nitrogen Resilience in Waterlogged Soybean plants
- Cell Senescence in Type II Diabetes: Therapeutic Potential
- Transgene-Free Canker-Resistant Citrus sinensis with Cas12/RNP
- AI Literacy in Early Childhood Education: Challenges and Opportunities
One thought on “Understanding the impact of SARS-CoV-2 by studying similar viruses”