Zika Virus Molecular Evolution Explained by Near Neutral Balanced Selectionist Theory
Document Type
Poster
College
College of Science & Mathematics
Start Date
25-3-2026 1:00 PM
End Date
25-3-2026 2:00 PM
Abstract
The Zika virus (ZIKV) Asian and American lineages causes severe neuroses in humans and no FDA-approved vaccine or antiviral is available. Mice model infection studies suggest the Asian and American ZIKV lineages are more fit than its older African lineage. Fitting evolutionary frameworks to genomic analysis and identifying adaptive mutations can enhance our understanding of ZIKV molecular evolution and expedite antiviral and vaccine development. We applied our novel substitution-mutation rate ratio (c/µ) framework to 884 ZIKV genomic sequences to 1) identify adaptive mutation sites altering protein phenotype (nonsynonymous protein mutations) and potentially altering protein expression (synonymous protein and regulatory mutations) and 2) to elucidate the combined interplay of natural selection and genetic drifting forces on its molecular evolution. Numerous adaptive mutations (c/µ > 1) were consistent with their reported enhanced pathogenicity and neurovirulence phenotypes in the literature. Synonymous mutations in protein and regulatory regions modulate nucleic acid structure stability and could shape codon usage and protein expression. Moreover, the ZIKV genome and genes exhibited an L-shaped c/µ distribution of fitness effects (DFE) with mixed observance of the time-independent substitution rate (molecular clock). These results are consistent with the Nearly-Neutral Selectionist Theory (NNST) instead of Kimura’s Neutral Theory (KNT) or Selectionist Theory (ST). ZIKV molecular evolution seems to be largely shaped by symmetric balancing of nearly neutral selection with episodic natural selection via adaptive mutations. Interestingly, this balanced selection mechanism in the Asian and American lineages could help explain how ZIKV maintains the less lethal neurovirulent phenotype that causes infant microcephaly, compared with the African lineage, which is more neurovirulent and often terminates the developing fetus, contributing towards an evolutionary dead-end for this virus.
Zika Virus Molecular Evolution Explained by Near Neutral Balanced Selectionist Theory
The Zika virus (ZIKV) Asian and American lineages causes severe neuroses in humans and no FDA-approved vaccine or antiviral is available. Mice model infection studies suggest the Asian and American ZIKV lineages are more fit than its older African lineage. Fitting evolutionary frameworks to genomic analysis and identifying adaptive mutations can enhance our understanding of ZIKV molecular evolution and expedite antiviral and vaccine development. We applied our novel substitution-mutation rate ratio (c/µ) framework to 884 ZIKV genomic sequences to 1) identify adaptive mutation sites altering protein phenotype (nonsynonymous protein mutations) and potentially altering protein expression (synonymous protein and regulatory mutations) and 2) to elucidate the combined interplay of natural selection and genetic drifting forces on its molecular evolution. Numerous adaptive mutations (c/µ > 1) were consistent with their reported enhanced pathogenicity and neurovirulence phenotypes in the literature. Synonymous mutations in protein and regulatory regions modulate nucleic acid structure stability and could shape codon usage and protein expression. Moreover, the ZIKV genome and genes exhibited an L-shaped c/µ distribution of fitness effects (DFE) with mixed observance of the time-independent substitution rate (molecular clock). These results are consistent with the Nearly-Neutral Selectionist Theory (NNST) instead of Kimura’s Neutral Theory (KNT) or Selectionist Theory (ST). ZIKV molecular evolution seems to be largely shaped by symmetric balancing of nearly neutral selection with episodic natural selection via adaptive mutations. Interestingly, this balanced selection mechanism in the Asian and American lineages could help explain how ZIKV maintains the less lethal neurovirulent phenotype that causes infant microcephaly, compared with the African lineage, which is more neurovirulent and often terminates the developing fetus, contributing towards an evolutionary dead-end for this virus.