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Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs.

ABSTRACT: SARS-CoV2 virus is believed to be originated from a closely related bat Coronavirus RaTG13 lineage and uses its key entry-point residues in S1 protein to attach with human ACE2 receptor. SARS-CoV2 could enter human from bat with its poorly developed entry-point residues much before its known appearance with slower mutation rate or recently with efficiently developed entry-point residues with higher mutation rate or through an intermediate host. Temporal analysis of SARS-CoV2 genome shows that its nucleotide substitution rate is as low as 27nt/year with an evolutionary rate of 9×10^-4/site/year, which is well within the range of other RNA virus (10^-4 to 10^-6/site/year). TMRCA of SARS-CoV2 from bat RaTG13 lineage appears to be in between 9 and 14 years. Evolution of a critical entry-point residue Y493Q needs two substitutions with an intermediate virus carrying Y493H (Y>H>Q) but has not been identified in known twenty-nine bat CoV virus. Genetic codon analysis indicates that SARS-CoV2 evolution during propagation in human disobeys neutral evolution as nonsynonymous mutations surpass synonymous mutations with the increase of ω (d_n/d_s). Taken together, genetic data suggests that SARS-CoV2 is originated long time back before its appearance in human in 2019. Increase of ω signifies that SARs-CoV2 evolution is approaching towards diversifying selection from purifying selection predictably for its infection power to evade multiple human organs.

SUBMITTER: Maiti AK

PROVIDER: S-EPMC8843322 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs.

Maiti Amit K AK

Virus research 20220215

SARS-CoV2 virus is believed to be originated from a closely related bat Coronavirus RaTG13 lineage and uses its key entry-point residues in S1 protein to attach with human ACE2 receptor. SARS-CoV2 could enter human from bat with its poorly developed entry-point residues much before its known appearance with slower mutation rate or recently with efficiently developed entry-point residues with higher mutation rate or through an intermediate host. Temporal analysis of SARS-CoV2 genome shows that it ...[more]

PMID: 35176330

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Project description:BackgroundThe bacterial flagellum is the most important organelle of motility in bacteria and plays a key role in many bacterial lifestyles, including virulence. The flagellum also provides a paradigm of how hierarchical gene regulation, intricate protein-protein interactions and controlled protein secretion can result in the assembly of a complex multi-protein structure tightly orchestrated in time and space. As if to stress its importance, plants and animals produce receptors specifically dedicated to the recognition of flagella. Aside from motility, the flagellum also moonlights as an adhesion and has been adapted by humans as a tool for peptide display. Flagellar sequence variation constitutes a marker with widespread potential uses for studies of population genetics and phylogeny of bacterial species.ResultsWe sequenced the complete flagellin gene (flaA) in 18 different species and subspecies of Aeromonas. Sequences ranged in size from 870 (A. allosaccharophila) to 921 nucleotides (A. popoffii). The multiple alignment displayed 924 sites, 66 of which presented alignment gaps. The phylogenetic tree revealed the existence of two groups of species exhibiting different FlaA flagellins (FlaA1 and FlaA2). Maximum likelihood models of codon substitution were used to analyze flaA sequences. Likelihood ratio tests suggested a low variation in selective pressure among lineages, with an omega ratio of less than 1 indicating the presence of purifying selection in almost all cases. Only one site under potential diversifying selection was identified (isoleucine in position 179). However, 17 amino acid positions were inferred as sites that are likely to be under positive selection using the branch-site model. Ancestral reconstruction revealed that these 17 amino acids were among the amino acid changes detected in the ancestral sequence.ConclusionThe models applied to our set of sequences allowed us to determine the possible evolutionary pathway followed by the flaA gene in Aeromonas, suggesting that this gene have probably been evolving independently in the two groups of Aeromonas species since the divergence of a distant common ancestor after one or several episodes of positive selection.ReviewersThis article was reviewed by Alexey Kondrashov, John Logsdon and Olivier Tenaillon (nominated by Laurence D Hurst).

Project description:High-throughput sequencing enables rapid genome sequencing during infectious disease outbreaks and provides an opportunity to quantify the evolutionary dynamics of pathogens in near real-time. One difficulty of undertaking evolutionary analyses over short timescales is the dependency of the inferred evolutionary parameters on the timespan of observation. Crucially, there are an increasing number of molecular clock analyses using external evolutionary rate priors to infer evolutionary parameters. However, it is not clear which rate prior is appropriate for a given time window of observation due to the time-dependent nature of evolutionary rate estimates. Here, we characterize the molecular evolutionary dynamics of SARS-CoV-2 and 2009 pandemic H1N1 (pH1N1) influenza during the first 12 months of their respective pandemics. We use Bayesian phylogenetic methods to estimate the dates of emergence, evolutionary rates, and growth rates of SARS-CoV-2 and pH1N1 over time and investigate how varying sampling window and data set sizes affect the accuracy of parameter estimation. We further use a generalized McDonald-Kreitman test to estimate the number of segregating nonneutral sites over time. We find that the inferred evolutionary parameters for both pandemics are time dependent, and that the inferred rates of SARS-CoV-2 and pH1N1 decline by ∼50% and ∼100%, respectively, over the course of 1 year. After at least 4 months since the start of sequence sampling, inferred growth rates and emergence dates remain relatively stable and can be inferred reliably using a logistic growth coalescent model. We show that the time dependency of the mean substitution rate is due to elevated substitution rates at terminal branches which are 2-4 times higher than those of internal branches for both viruses. The elevated rate at terminal branches is strongly correlated with an increasing number of segregating nonneutral sites, demonstrating the role of purifying selection in generating the time dependency of evolutionary parameters during pandemics.

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Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs.

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Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs.

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