Journal of infection in developing countries · 2026
Clock-like behavior across Orthoebolavirus species suggests alternative evolution of the 2026 Bundibugyo virus outbreak.
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Sganzerla Martinez Gustavo, Kumar Anuj, Dutt Mansi, Wayengera Misaki, Sabiiti Wilber, Kelvin David J, Kyobe Bosa Henry
Аннотация
INTRODUCTION: Recent increase in reported cases of Bundibugyo virus (species Orthoebolavirus bundibugyoense) in the Democratic Republic of the Congo and Uganda highlight the importance of understanding their evolutionary dynamics.
METHODOLOGY: We analyzed publicly available genomes obtained from the Pathoplexus database representing 3 medically relevant species of the Orthoebolavirus genus: Ebola virus (n = 3,388), Zaire virus (n = 166), and Bundibugyo virus (n = 49). We investigated whether genetic divergence is associated with sampling time utilizing root-to-tip regression analyses derived from temporally calibrated phylogenies as an indicator of molecular clock behavior.
RESULTS: Sudan virus (R2 = 0.855) and Ebola virus (R2 = 0.709) exhibited significant temporal structures between sampling time and genetic divergence. Bundibugyo virus displayed strong clock-like behavior after exclusion of 2026 genomes (R2 = 0.983), which showed a marked substitution deficit relative to the historical molecular clock and deviated substantially from the inferred regression. Date randomization tests supported the presence of temporal signal across all datasets (p < 0.001), indicating that the temporal signals exceeded expectations under a null model without temporal structure.
CONCLUSIONS: These results provide a comparative assessment of the temporal structures across 3 medically relevant Orthoebolavirus species. While historical genomes largely conformed to molecular clock expectations, the inclusion of genomes from the ongoing 2026 Bundibugyo virus outbreak deviated from these projections, suggesting an alternative evolutionary process for 2026 Bundibugyo virus, such as viral persistence in immune-privileged anatomical sites of previously infected individuals or an independent zoonotic spillover event in an alternative species, in which the virus evolved within its natural reservoir prior to human infection.
METHODOLOGY: We analyzed publicly available genomes obtained from the Pathoplexus database representing 3 medically relevant species of the Orthoebolavirus genus: Ebola virus (n = 3,388), Zaire virus (n = 166), and Bundibugyo virus (n = 49). We investigated whether genetic divergence is associated with sampling time utilizing root-to-tip regression analyses derived from temporally calibrated phylogenies as an indicator of molecular clock behavior.
RESULTS: Sudan virus (R2 = 0.855) and Ebola virus (R2 = 0.709) exhibited significant temporal structures between sampling time and genetic divergence. Bundibugyo virus displayed strong clock-like behavior after exclusion of 2026 genomes (R2 = 0.983), which showed a marked substitution deficit relative to the historical molecular clock and deviated substantially from the inferred regression. Date randomization tests supported the presence of temporal signal across all datasets (p < 0.001), indicating that the temporal signals exceeded expectations under a null model without temporal structure.
CONCLUSIONS: These results provide a comparative assessment of the temporal structures across 3 medically relevant Orthoebolavirus species. While historical genomes largely conformed to molecular clock expectations, the inclusion of genomes from the ongoing 2026 Bundibugyo virus outbreak deviated from these projections, suggesting an alternative evolutionary process for 2026 Bundibugyo virus, such as viral persistence in immune-privileged anatomical sites of previously infected individuals or an independent zoonotic spillover event in an alternative species, in which the virus evolved within its natural reservoir prior to human infection.