An unprecedented amount of genomic sequence data is accumulating in real-time during the COVID-19 pandemic. More than 1.2 million sequences of SARS-CoV-2 have been created over the past fifteen months, and the scientific community has gained a lot of knowledge from these sequences.
Of all the mutations sampled so far, only a few have appeared in the viral count. Several of these mutations have appeared recently and in multiple strains. This is a biblical example of convergent evolution at the molecular level that generates curiosity and also acts as a catalyst for studying the basis of the adaptive feature driving these events.
A recent report issued as a preliminary print on bioRxiv* A server, by a team of researchers focused on the extent of convergent evolution of the SARS-CoV-2 spike (S) protein. The report confirms that the major strains of SARS-CoV-2 of concern have the most closely related spike protein mutations. This indicates their primary adaptive feature.
Analysis of the convergent evolutionary range of the SARS-CoV-2 spike (S) protein.
The vast majority of spike protein sites – 21 of 25 – under convergent evolution are tightly clustered into 3 functional domains – the receptor-binding domain (RBD), the N-terminal domain, and the Furin cleavage site. The study also shows that among the incentive mutations associated with elevated protein receptors, alternatives that enhance ACE2 affinity are preferred.
The researchers write:
To monitor the evolution of SARS-CoV-2, we briefly searched for convergent changes among all the genes of the SARS-CoV-2 genome in NextStrain. “
While the mutation space analyzed in the spike protein was all amino acids accessible by single nucleotide changes (SNCs), substitutions requiring two nucleotide changes or cognitive mutations of multiple residues began to emerge only recently.
Vaccination efforts may shift the evolutionary pressure of SARS-CoV-2 toward immune escape mutation at the expense of viral fitness
SARS-CoV-2, like other viruses, has the evolutionary pressure to increase the fitness of the virus in a new environment. However, global vaccination programs are expected to shift the pressure toward an immune escape boom, even at the expense of viral fitness.
The results of this study show that among the vast number of mutations discovered in the SARS-CoV-2 genomes, only a few have risen to high frequencies. Interestingly, many of these mutations exhibit convergent evolution, indicating a strong adaptive feature conferred by specific mutations.
Most of the affinity-enhancing mutations that can be accessed by cancer stem cells have already been seen abundantly in the global genomic dataset. In contrast, the study identified only one mutation – Y505W – with relatively high representativeness and enhanced affinity performance compared to the wild mutation requiring two nucleotide changes. Several mutations requiring two nucleotide changes with stronger binding to ACE2 have not yet been sampled.
The convergent evolution of the spike protein could help produce more effective second-generation global vaccines to protect the world’s population
The 2 nucleotide changes sampled thus far show a significant increase in the wealth of these advanced mutations over the past three months, although very low frequencies have persisted. This explains to why cognitive mutations that require coordinated changes to the many nucleotides in the protein remain scarce.
The ability to predict the convergent evolution of the spike protein can increase the probabilities of spiky protein sequences in global second-generation vaccines, effectively protecting the world population from current and future viral variants of concern.
Despite the physical association and the convergent appearance of these adaptive mutations, they are not well understood. The researchers aim to advance the research into variables that are currently in circulation that are not well studied and may become variables of concern in the future.
The team concludes:
Our analysis shows that among the vast number of mutations discovered in the SARS-CoV-2 genomes, only a few have risen to the high frequencies. “
bioRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive or directing clinical practice / health-related behavior or treated as static information.