Examining the molecular clock hypothesis for the contemporary evolution of the rabies virus

• DOI: 10.1371/journal.ppat.1012740
• Publication Date: 2024-11-25T18:43:59Z
• Authors: Rowan Durrant; Christina A. Cobbold; Kirstyn Brunker; Kathryn Campbell; Jonathan Dushoff; Elaine A. Ferguson; Gurdeep Jaswant; Ahmed Lugelo; Kennedy Lushasi; Lwitiko Sikana; Katie Hampson
• Keywords: Viral evolution; Lyssavirus; Molecular clock

The molecular clock hypothesis assumes that mutations accumulate on an organism's genome at a constant rate over time, but this assumption does not always hold true. While modelling approaches exist to accommodate deviations from strict clock, assumptions about variation may fully represent the underlying evolutionary processes. There is considerable variability in rabies virus (RABV) incubation periods, ranging days year, during which viral replication be reduced. This prompts question of whether RABV per infection generation basis might more appropriate. We investigate how variable periods affect root-to-tip divergence under per-unit time and per-generation models mutation. Additionally, we assess well these time-stamped sequences. find low substitution rates (<1 generation) patterns between are difficult distinguish, while above threshold differences become apparent across range sampling rates. Using Tanzanian dataset, calculate mean 0.17 substitutions generation. At RABV's rate, model unlikely evolution substantially differently than when examining contemporary outbreaks; enough generations for any accumulate, extreme average out. However, measuring holds potential applications such as inferring transmission trees predicting lineage emergence.