Moderate Amounts of Epistasis are Not Evolutionarily Stable in Small Populations

Sydykova, Dariya K.; LaBar, Thomas; Adami, Christoph; Wilke, Claus O.

doi:10.1007/s00239-020-09942-4

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…Because knowledge about the DFE is necessary to understand the evolutionary dynamics of populations, techniques to quantify it from empirical data have been developed 50 . DFE modifiers have also been studied theoretically, albeit in other contexts 56 , 57 . For example, theory predicts that DFE modifiers that render mutations more deleterious may help drive viral populations to extinction 56 .…”

Section: Discussionmentioning

confidence: 99%

Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein

Wagner

2023

Nat Commun

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Can evolvability—the ability to produce adaptive heritable variation—itself evolve through adaptive Darwinian evolution? If so, then Darwinian evolution may help create the conditions that enable Darwinian evolution. Here I propose a framework that is suitable to address this question with available experimental data on adaptive landscapes. I introduce the notion of an evolvability-enhancing mutation, which increases the likelihood that subsequent mutations in an evolving organism, protein, or RNA molecule are adaptive. I search for such mutations in the experimentally characterized and combinatorially complete fitness landscapes of a protein and an RNA molecule. I find that such evolvability-enhancing mutations indeed exist. They constitute a small fraction of all mutations, which shift the distribution of fitness effects of subsequent mutations towards less deleterious mutations, and increase the incidence of beneficial mutations. Evolving populations which experience such mutations can evolve significantly higher fitness. The study of evolvability-enhancing mutations opens many avenues of investigation into the evolution of evolvability.

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Section: Discussionmentioning

confidence: 99%

Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein

Wagner

2023

Nat Commun

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“…A DFE modifier is a specific form of epistasis (i.e., the genetic-background dependence of mutational effects), where the modifier allele alters mutational effects genome-wide. Sydykova et al (52) have recently explored a related model of tunable epistasis, in which they found that epistasis can evolve in different directions under high mutation rates. Whether weakening the effects of deleterious mutations can lead to survival has been modeled in the research area of quasi-species theory, where a so-called "error threshold" determines the condition in which mutation overwhelms selection (e.g., for finite populations, 53,54).…”

Section: Rethinking 'Beneficial' Mutationsmentioning

confidence: 99%

Evolutionary models predict potential mechanisms of escape from mutational meltdown

2022

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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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“…Consequently,

and

play a crucial role during evolutionary adaptation but are also the consequence of evolution. However, whether or not an increase or decrease in

makes organisms more or less robust is still highly debated [ 33 , 34 , 35 , 36 , 37 , 38 ]. What likely made answering this question hard is not only the difficulty one faces when doing evolutionary experiments with natural organisms but also the way how computational models were made.…”

Section: Introductionmentioning

confidence: 99%

Reducing Epistasis and Pleiotropy Can Avoid the Survival of the Flattest Tragedy

Mehra,

Hintze

2024

Biology

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This study investigates whether reducing epistasis and pleiotropy enhances mutational robustness in evolutionary adaptation, utilizing an indirect encoded model within the “survival of the flattest” (SoF) fitness landscape. By simulating genetic variations and their phenotypic consequences, we explore organisms’ adaptive mechanisms to maintain positions on higher, narrower evolutionary peaks amidst environmental and genetic pressures. Our results reveal that organisms can indeed sustain their advantageous positions by minimizing the complexity of genetic interactions—specifically, by reducing the levels of epistasis and pleiotropy. This finding suggests a counterintuitive strategy for evolutionary stability: simpler genetic architectures, characterized by fewer gene interactions and multifunctional genes, confer a survival advantage by enhancing mutational robustness. This study contributes to our understanding of the genetic underpinnings of adaptability and robustness, challenging traditional views that equate complexity with fitness in dynamic environments.

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Moderate Amounts of Epistasis are Not Evolutionarily Stable in Small Populations

Cited by 6 publications

References 49 publications

Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein

Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein

Evolutionary models predict potential mechanisms of escape from mutational meltdown

Reducing Epistasis and Pleiotropy Can Avoid the Survival of the Flattest Tragedy

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