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Published on: June 14, 2022
Positive natural selection in the evolution of human metapneumovirus attachment glycoprotein
Abinash Padhi1, Bindhu Verghese
1Department of Biological Science, University of Tulsa, 600 S. College Ave. Tulsa, OK 74104, USA. abinash-padhi@utulsa.edu
Abstract:
Human metapneumovirus (hMPV), a newly discovered virus of the family Paramyxoviridae, has been associated with upper and lower respiratory tract infections in different age groups in many countries. The putative attachment (G) glycoprotein of this virus was previously reported to have shown more extensive nucleotide and deduced amino acid sequence polymorphism than any other genomic regions of this virus, leading to four sub-lineages. Using a maximum likelihood-based codon substitution model of sequence evolution, here we report that sequences of extracellular domain of 8 amino acid sites in lineage 1a, and 3 amino acid sites each in lineage 1b, 2a, and 2b have a higher rate of nonsynonymous substitutions (d(N)) than the synonymous substitutions (d(S)) with a posterior probability above 0.95, thus suggesting the evidence of adaptive evolution driven by Darwinian selection. Although it is unclear whether these amino acid adaptations are driven by differential immune pressure or some other factors, identification of these positively selected amino acid sites would help in better screening using epitope mapping technology to identify and localize the sites that can be recognized by the immune system. We also observed surprisingly higher nucleotide substitution rates per site, per year for each lineage of hMPV than the rates that were previously reported for the human respiratory syncytial virus, suggesting rapid evolutionary dynamics of hMPV.
Insights
Human metapneumovirus (hMPV) shows rapid evolution, with specific G glycoprotein sites undergoing adaptive evolution. Identifying these sites aids in understanding immune responses and developing targeted interventions for hMPV infections.
Area of Science:
- Virology
- Evolutionary Biology
- Immunology
Background:
- Human metapneumovirus (hMPV), a Paramyxoviridae family member, causes respiratory infections globally.
- The hMPV G glycoprotein exhibits significant sequence polymorphism, defining four distinct sub-lineages.
- Previous studies indicated high variability in the hMPV G protein, suggesting potential adaptive evolution.
Purpose of the Study:
- To investigate adaptive evolution in the hMPV G glycoprotein using computational methods.
- To identify specific amino acid sites under positive selection in different hMPV lineages.
- To compare evolutionary rates of hMPV with other respiratory viruses like human respiratory syncytial virus (hRSV).
Main Methods:
- Utilized a maximum likelihood-based codon substitution model to analyze sequence evolution.
- Compared rates of nonsynonymous (dN) and synonymous (dS) substitutions across hMPV lineages.
- Analyzed extracellular domain sequences of the G glycoprotein.
Main Results:
- Identified 8 amino acid sites in lineage 1a and 3 sites each in lineages 1b, 2a, and 2b with dN/dS > 1 and posterior probability > 0.95, indicating positive selection.
- Observed significantly higher nucleotide substitution rates per site per year for hMPV lineages compared to hRSV.
- Confirmed evidence of Darwinian selection driving amino acid adaptations in the hMPV G glycoprotein.
Conclusions:
- Specific amino acid sites in the hMPV G glycoprotein are under positive adaptive evolution.
- The rapid evolutionary dynamics of hMPV, evidenced by high substitution rates, warrant further investigation.
- Identifying positively selected sites can facilitate epitope mapping for improved diagnostics and vaccine development targeting hMPV.
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