RT Journal Article
SR Electronic
T1 Why are viral genomes so fragile? The bottleneck hypothesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.23.427881
DO 10.1101/2021.01.23.427881
A1 Nono S. C. Merleau
A1 Sophie Pénisson
A1 Philip J. Gerrish
A1 Santiago F. Elena
A1 Matteo Smerlak
YR 2021
UL http://biorxiv.org/content/early/2021/01/23/2021.01.23.427881.abstract
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.