Scaling properties of evolutionary paths in a biophysical model of protein adaptation

Manhart, Michael; Morozov, Alexandre V.

doi:10.1088/1478-3975/12/4/045001

Cited by 5 publications

(3 citation statements)

References 48 publications

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“…These studies reveal that effects of multiple mutations on protein energetics are nearly additive, especially if the mutations are distant from each other in the linear sequence [35]. Consequently, the assumption of independent energetic contributions of residues at different sites has been extensively used in biophysical models of protein evolution that express organismal fitness in terms of protein energetics [30,[36][37][38][39]. In the light of these previous findings, we expected Michaelis-Menten free energies to be approximately additive as well, with two-aa coupling terms playing a secondary role.…”

Section: Discussionmentioning

confidence: 99%

Sparse Epistatic Patterns in the Evolution of Terpene Synthases

Ballal

Laurendon

Salmon

et al. 2020

Molecular Biology and Evolution

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We explore sequence determinants of enzyme activity and specificity in a major enzyme family of terpene synthases. Most enzymes in this family catalyze reactions that produce cyclic terpenes—complex hydrocarbons widely used by plants and insects in diverse biological processes such as defense, communication, and symbiosis. To analyze the molecular mechanisms of emergence of terpene cyclization, we have carried out in-depth examination of mutational space around (E)-β-farnesene synthase, an Artemisia annua enzyme which catalyzes production of a linear hydrocarbon chain. Each mutant enzyme in our synthetic libraries was characterized biochemically, and the resulting reaction rate data were used as input to the Michaelis–Menten model of enzyme kinetics, in which free energies were represented as sums of one-amino-acid contributions and two-amino-acid couplings. Our model predicts measured reaction rates with high accuracy and yields free energy landscapes characterized by relatively few coupling terms. As a result, the Michaelis–Menten free energy landscapes have simple, interpretable structure and exhibit little epistasis. We have also developed biophysical fitness models based on the assumption that highly fit enzymes have evolved to maximize the output of correct products, such as cyclic products or a specific product of interest, while minimizing the output of byproducts. This approach results in nonlinear fitness landscapes that are considerably more epistatic. Overall, our experimental and computational framework provides focused characterization of evolutionary emergence of novel enzymatic functions in the context of microevolutionary exploration of sequence space around naturally occurring enzymes.

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Section: Discussionmentioning

confidence: 99%

Sparse Epistatic Patterns in the Evolution of Terpene Synthases

Ballal

Laurendon

Salmon

et al. 2020

Molecular Biology and Evolution

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“…Once this is tested, and if proved, it can be checked whether any deviation from the prevalent condition manifests itself as a pathology. Besides, proteins evolve new binding interactions while maintaining stability during their size-scaling (Manhart & Morozov, 2015). Those new binding interactions might contribute to our understanding in inter-tissue variations and functionalities, where different-sized proteins are distinctively expressed.…”

Section: Insightsmentioning

confidence: 99%

Information‐theoretic approach in allometric scaling relations of DNA and proteins

Adıgüzel

2021

Chem Biol Drug Des

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Allometric scaling relations correlate biological parameters, such as the drug clearances and interspecies physiological parameters (Huang et al., 2015), or cell volumes and genome sizes. Size of the cellular genome, in terms of the nuclear volume, is known to be related to the size of the cell (Sachs, 1983). However, the underlying mechanisms of this relation and its further implications are unknown (Doyle & Coate, 2019). It is also correlated with cellular metabolism. For instance, it has recently been reported that genome/cell size affects photosynthetic

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“…Relatedly, increasing cardinality not only increases the number of extra-dimensional bypasses to the global peak, but also to local peaks [9,33], so whether evolving populations converge on the global or local peaks will depend on how these bypasses influence the relative sizes of the basins of attraction of these peaks. Finally, because extra-dimensional bypasses are by definition longer than direct paths, they are less likely to be utilized by evolving populations [34], which may instead follow direct accessible paths to emerging local peaks. Thus, calling a fitness landscape accessible based on the existence of at least one accessible path to the global peak [24,26,27] may belie a landscape's true accessibility.…”

Section: Introductionmentioning

confidence: 99%

Alphabet cardinality and adaptive evolution

Srivastava,

Rozhoňová,

Payne

2023

J. Phys. A: Math. Theor.

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One of the most fundamental characteristics of a fitness landscape is its dimensionality, which is defined by genotype length and alphabet cardinality—the number of alleles per locus. Prior work has shown that increasing landscape dimensionality can promote adaptation by forming new ‘uphill’ mutational paths to the global fitness peak, but can also frustrate adaptation by increasing landscape ruggedness. How these two topographical changes interact to influence adaptation is an open question. Here, we address this question in the context of alphabet cardinality, using theoretical fitness landscapes with tuneable fitness correlations, as well as three empirical fitness landscapes for proteins. We find that the primary effect of increasing alphabet cardinality is the introduction of a new global fitness peak. Controlling for this effect, we find that increasing alphabet cardinality promotes adaptation on uncorrelated fitness landscapes, but frustrates adaptation on correlated fitness landscapes. The primary explanation is that the increased ruggedness that accompanies alphabet expansion is characterized by an increase in mean peak height on uncorrelated fitness landscapes, but a decrease in mean peak height in correlated fitness landscapes. Moreover, in two of the empirical fitness landscapes we observe no effect of increasing alphabet cardinality on adaptation, despite an increase in the number of peaks and a decrease in mean peak height, calling into question the utility of these common measures of landscape ruggedness as indicators of evolutionary outcomes.

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Scaling properties of evolutionary paths in a biophysical model of protein adaptation

Cited by 5 publications

References 48 publications

Sparse Epistatic Patterns in the Evolution of Terpene Synthases

Sparse Epistatic Patterns in the Evolution of Terpene Synthases

Information‐theoretic approach in allometric scaling relations of DNA and proteins

Alphabet cardinality and adaptive evolution

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