Why are viral genomes so fragile? The bottleneck hypothesis

Merleau, Nono S. C.; Pénisson, Sophie; Gerrish, Philip J.; Elena, Santiago F.; Smerlak, Matteo

doi:10.1371/journal.pcbi.1009128

Cited by 9 publications

(14 citation statements)

References 62 publications

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“…This leads to the inability of a population to maintain its genetic information, which can in general be considered similar to mutational meltdown (56, but see 57). Moreover, the evolution of more severe effects of deleterious mutations has been theoretically studied with respect to models of drift robustness (58), quasi-species evolution (e.g., 59) and epidemiology (60).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary models predict potential mechanisms of escape from mutational meltdown

Bank

Schmitz

Morales‐Arce

2022

Preprint

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Mutagenic drugs are promising candidates for the treatment of various RNA virus infections. Increasing the mutation rate of the virus leads to rapid accumulation of deleterious mutation load, which is proposed to ultimately result in extinction as described by the theoretical concepts of mutational meltdown and lethal mutagenesis. However, the conditions and potential mechanisms of viral escape from the effects of mutagenic drugs have not been conceptually explored. Here we apply a computational approach to quantify the population dynamics and genetics of a population under high mutation rates and discuss the likelihood of adaptation to a mutagenic drug by means of three proposed mechanisms: (1) a proportion of "traditional" beneficial mutations that increase growth/fitness, (2) a mutation rate modifier (i.e., evolution of resistance to the mutagenic drug) that reduces the mutation rate, and (3) a modifier of the distribution of fitness effects, which either decreases or increases deleterious effects of mutations (i.e., evolution of tolerance to the mutagenic drug). We track the population dynamics and genetics of evolving populations and find that successful adaptations have to appear early to override the increasing mutational load and rescue the population from its imminent extinction. We highlight that the observed stochasticity of adaptation, especially by means of modifiers of the distribution of fitness effects, is difficult to capture in experimental trials, which may leave potential dangers of the use of mutagenic treatments unexposed.

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Section: Discussionmentioning

confidence: 99%

Evolutionary models predict potential mechanisms of escape from mutational meltdown

Bank

Schmitz

Morales‐Arce

2022

Preprint

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“…Viruses exist as a cloud of related sequences, called a quasispecies, rather than a single consensus [23][24][25]. This genetic variation is the basis for the evolution and adaptation of viruses to hosts, vectors, or their environment [83]. During normal replication, genetic variation is generated through mutation, reassortment, and recombination (Figure 3).…”

Section: Variation Bottlenecks Genetic Drift and Selection Pressure I...mentioning

confidence: 99%

Determinants of Virus Variation, Evolution, and Host Adaptation

LaTourrette

García-Ruíz

2022

Pathogens

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Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to genetic drift and selection pressures by host and vector factors, and random variants or those with a competitive advantage are fixed in the population and mediate the emergence of new viral strains or species with novel biological properties. This process creates a footprint in the virus genome evident as the preferential accumulation of substitutions, insertions, or deletions in areas of the genome that function as determinants of host adaptation. Here, with respect to plant viruses, we review the current understanding of the sources of variation, the effect of selection, and its role in virus evolution and host adaptation.

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“…In other words, the fire of infection burns fast but extinguishes easily. To reach the next clique or cluster, the epidemic has to pass via narrow population bottlenecks, where only a few pathogens can pass, so that details matter and chance rules [52]. (This "reign of small numbers" [1] plays a prominent role in virus evolution, as discussed further below.…”

Section: Heterogeneous Contact Networkmentioning

confidence: 99%

“…Put simply, having too many mutations in a genome, most of which will be deleterious or at best neutral, can drive a population to extinction ("Muller's ratchet"). But also too few mutations can cause extinction, namely by rendering a population unable to survive changes in the environment, and to recover its genetic diversity after drastic population reductions in bottlenecks [52]. Quasispecies evolution thus allows fast mutating microbes to strike an optimum balance between evolvability and structural preservation [19].…”

Section: Survival Of the Flattest And The Flumentioning

confidence: 99%