PT  - JOURNAL ARTICLE
AU  - Nono S. C. Merleau
AU  - Sophie Pénisson
AU  - Philip J. Gerrish
AU  - Santiago F. Elena
AU  - Matteo Smerlak
TI  - Why are viral genomes so fragile? The bottleneck hypothesis
AID  - 10.1101/2021.01.23.427881
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.23.427881
4099  - http://biorxiv.org/content/early/2021/01/23/2021.01.23.427881.short
4100  - http://biorxiv.org/content/early/2021/01/23/2021.01.23.427881.full
AB  - If they undergo new mutations at each replication cycle, why are RNA viral genomes so fragile, with most mutations being either strongly deleterious or lethal? Here we provide theoretical evidence for the hypothesis that genetic fragility evolves as a consequence of the pervasive population bottlenecks experienced by viral populations at various stages of their life cycles. Modelling within-host viral populations as multi-type branching processes, we show that mutational fragility lowers the rate at which Muller’s ratchet clicks and increases the survival probability through multiple bottlenecks. In the context of a susceptible-exposed-infectious-recovered epidemiological model, we find that the attack rate of fragile viral strains can exceed that of more robust strains, particularly at low infectivities and high mutation rates. Our findings highlight the importance of demographic events such as transmission bottlenecks in shaping the genetic architecture of viral pathogens.Competing Interest StatementThe authors have declared no competing interest.