Location
Chamberlain Student Center
Document Type
Poster
College
College of Science & Mathematics
Event Website
https://research.rowan.edu/rowan-research-days-2024.html
Start Date
26-3-2024 12:00 PM
End Date
26-3-2024 3:00 PM
Abstract
Virus pandemics have significantly impacted human welfare and development. Understanding the true molecular evolution of viruses is critical for preventing future pandemics and developing the next-generation drugs and vaccines. Unfortunately, viruses exhibiting constant genomic substitution rates (GSRs) despite increasing vaccinations and human infections (SARS-CoV-2) and viruses under seemingly extreme conservation (ZIKV) paints a confusing picture of viral evolution, and the main evolutionary theories (Selectionist Theory, Kimura’s Neutral Theory) cannot explain their molecular evolution. Here, we developed a first-principle model, c/u, to characterize reproductive fitness changes in viruses based on variations in the nucleotide/codon mutation rate (c) with respect to the global genomic mutation rate (u). c/u is nucleotide-centric, since phenotypic changes in proteins are reflected by genotypic changes in genes. c/u can assign selection types to coding regions (virus function) and non-coding untranslated regions (UTRs, virus gene regulation). Additionally, c/u can handle conserved sites (c/u=0) and sites with few mutations under false positive selection (c/u<<>>1). The constant GSRs of SARS-CoV-2 and ZIKV are seemingly under effective neutral selection (c/u=1), indicating no advantageous/disadvantageous fitness change. Yet, the L-shaped probability distribution of c/u for a NT site indicates high sequence conservation, with higher c/u values being increasingly uncommon. Varying nucleotide and segment substitution rates were observed in both viruses, indicating a mixture of advantageous selection (c/u>1) and purifying selection (c/u
Near-Neutral Balanced Selection Theory (NNBST): Implication on the molecular evolution of SARS-CoV-2 and Zika virus
Chamberlain Student Center
Virus pandemics have significantly impacted human welfare and development. Understanding the true molecular evolution of viruses is critical for preventing future pandemics and developing the next-generation drugs and vaccines. Unfortunately, viruses exhibiting constant genomic substitution rates (GSRs) despite increasing vaccinations and human infections (SARS-CoV-2) and viruses under seemingly extreme conservation (ZIKV) paints a confusing picture of viral evolution, and the main evolutionary theories (Selectionist Theory, Kimura’s Neutral Theory) cannot explain their molecular evolution. Here, we developed a first-principle model, c/u, to characterize reproductive fitness changes in viruses based on variations in the nucleotide/codon mutation rate (c) with respect to the global genomic mutation rate (u). c/u is nucleotide-centric, since phenotypic changes in proteins are reflected by genotypic changes in genes. c/u can assign selection types to coding regions (virus function) and non-coding untranslated regions (UTRs, virus gene regulation). Additionally, c/u can handle conserved sites (c/u=0) and sites with few mutations under false positive selection (c/u<<>>1). The constant GSRs of SARS-CoV-2 and ZIKV are seemingly under effective neutral selection (c/u=1), indicating no advantageous/disadvantageous fitness change. Yet, the L-shaped probability distribution of c/u for a NT site indicates high sequence conservation, with higher c/u values being increasingly uncommon. Varying nucleotide and segment substitution rates were observed in both viruses, indicating a mixture of advantageous selection (c/u>1) and purifying selection (c/u
https://rdw.rowan.edu/grad_student_symposium/2024/mar26/5
Comments
Nicholas Paradis is a Ph.D. student in Pharmaceutical Chemistry working under Dr. Chun Wu.