Mutation bias and the predictability of evolution

Cano, Alejandro V.; Gitschlag, B.L.; Rozhoňová, Hana; Stoltzfus, Arlin; McCandlish, David M.; Payne, Joshua L.

doi:10.1098/rstb.2022.0055

Cited by 17 publications

(14 citation statements)

References 178 publications

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“…There is a growing body of literature that shows that mutation bias can be an important driver of adaptive outcomes (15,(51)(52)(53). Our results demonstrate that mutational biases can facilitate adaption, if they provide quick access to mutations conferring a trait under selection.…”

Section: Discussionmentioning

confidence: 61%

Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments

Flanagan

Horton

Taylor

2023

Preprint

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The observed mutational spectrum of adaptive outcomes can be constrained by many factors. For example, mutational biases can narrow the observed spectrum by increasing the rate of mutation at isolated sites in the genome. In contrast, complex environments can shift the observed spectrum by defining fitness consequences of mutational routes. We investigate the impact of different nutrient environments on the evolution of motility in the bacteria Pseudomonas fluorescens Pf0-2x (an engineered non-motile derivative of Pf0-1) in the presence and absence of a strong mutational hotspot. Previous work has shown that this mutational hotspot can be built and broken via six silent mutations, which provide rapid access to a mutation that rescues swimming motility and confers the strongest swimming phenotype in specific environments. Here, we evolved a hotspot and non-hotspot variant strain of Pf0-2x for motility under nutrient rich (LB) and nutrient limiting (M9) environmental conditions. We observed the hotspot strain consistently evolved faster across all environmental conditions and its mutational spectrum was robust to environmental differences. However, the non-hotspot strain had a distinct mutational spectrum that changed depending on the nutrient environment. Interestingly, while alternative adaptive mutations in nutrient-rich environments were equal to, or less effective than, the hotspot mutation, the majority of these mutations in nutrient-limited conditions produced superior swimmers. Our competition experiments mirrored these findings, underscoring the role of environment in defining both the mutational spectrum and the associated phenotype strength. This indicates that while mutational hotspots working in concert with natural selection can speed up access to robust adaptive mutations (which can provide a competitive advantage in evolving populations) they can limit exploration of the mutational landscape, restricting access to potentially stronger phenotypes in specific environments.

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Section: Discussionmentioning

confidence: 61%

Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments

Flanagan

Horton

Taylor

2023

Preprint

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“…Unlike previous work on burstiness on a genotypic level [25, 28], including interesting parallels to work on clusters of identical mutations originating from a premeiotic mutational events [72], our bursts are fundamentally a phenotypic effect that cannot be identified from sequences alone. There has been significant work showing that mutational biases can be observed in a wide range of organisms [73], but these effects are also seen at the sequence level. To illustrate, why bursts are a phenotypic effect, let us consider the schematic in Fig 1.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Non-Poissonian bursts in the arrival of phenotypic variation can strongly affect the dynamics of adaptation

Martin,

Schaper,

Camargo

et al. 2023

Preprint

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The introduction of novel phenotypic variation in a population through random mutations plays a crucial role in evolutionary dynamics. Here we show that, when the probability that a sequence has a particular phenotype in its 1-mutational neighbourhood is low, statistical fluctuations imply that in the weak-mutation or monomorphic regime, novel phenotypic variation is not introduced at a constant rate, but rather in non-Poissonian “bursts”. In other words, a novel phenotype appears multiple times in quick succession, or not at all for many generations. We use the RNA secondary-structure genotype-phenotype map to explore how increasing levels of heterogeneity in mutational neighbourhoods strengthen the bursts. Similar results are obtained for the HP model for protein tertiary structure and the Biomorphs model for morphological development. Burst can profoundly affect adaptive dynamics. Most notably, they imply that differences in arrival rates of novel variation can influence fixation rates more than fitness differences do.

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“…This parameter (average mutation rate per site) is, however, of little evolutionary relevance ( [11], as well as in forensics: see [12][13][14]), as it does not allow us to determine if the population is in equilibrium, or if allele frequencies will change, possibly reaching fixation. The relevant parameters enabling this prediction are the allele specific mutation rates, m1>2 and m2>1, and the analysis of the same data from this point of view is shown in Table 3.…”

Section: Duosmentioning

confidence: 99%

Mutation Rate (Under)estimation through Mendelian Incompatibilities

Amorim¹

2023

Hum Popul Genet Genom

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Mutation is the key player in evolutionary change, both in micro and macro scenarios. Defined as any hereditary change in the transmitted genome from progenitor to offspring, it embraces a heterogeneous set of phenomena, in terms of molecular bases and consequences.Here we limit our analyses to those corresponding to site-specific changes in nucleic acid sequence composition, without alteration in the genome size, i.e., substitutions. These analyses will be performed in the framework of the classical Mendelian diploid mode of transmission, without sex-linkage, under a simple Hardy-Weinberg model. Under these conditions, we show that: (i) per site mutation rates are evolutionarily uninformative, biallelically defined parameters being required to predict the genetic behavior of the population and are also essential to medical and forensic applications; (ii) at polymorphic sites (heterozygosity > 0), estimates of mutation rates through the simple counting of Mendelian incompatibilities in pedigrees are always underestimations, depending heavily on the allelic frequencies, a fact that may lead to erroneous evolutionary inferences, such as that (iii) apparently equal forward and reverse mutation rates, as estimated from Mendelian incompatibilities, do not equate to stable equilibrium. An approach allowing to correct the underestimation, by adopting a sequential strategy of allele specific estimation is presented.

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Mutation bias and the predictability of evolution

Cited by 17 publications

References 178 publications

Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments

Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments

Non-Poissonian bursts in the arrival of phenotypic variation can strongly affect the dynamics of adaptation

Mutation Rate (Under)estimation through Mendelian Incompatibilities

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