Network Context and Selection in the Evolution to Enzyme Specificity

Nam, Hojung; Lewis, Nathan E.; Lerman, Joshua A.; Lee, Dae-Hee; Chang, Roger L.; Kim, Donghyuk; Palsson, Bernhard Ø.

doi:10.1126/science.1216861

Cited by 258 publications

(252 citation statements)

References 75 publications

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“…Consequently, specialists require a much higher degree of maintenance than generalists that are promiscuous and multi-functional. This model study thus offered an explanation for why specialists have not replaced all the generalists in real organisms [421].…”

Section: Protein Evolution In the Context Of Functional Networkmentioning

confidence: 99%

Biophysics of protein evolution and evolutionary protein biophysics

Sikosek

Chan

2014

J. R. Soc. Interface.

220

207

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The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence-structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by 'hidden' conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution.

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Section: Protein Evolution In the Context Of Functional Networkmentioning

confidence: 99%

Biophysics of protein evolution and evolutionary protein biophysics

Sikosek

Chan

2014

J. R. Soc. Interface.

220

207

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“…Studies to explore the tRNA and protein-binding partners of E. coli ProXp-ST1 under different conditions are under way to help define the biological function of these proteins. It has been estimated that nearly 37% of E. coli enzymes are generalists with multiple substrates, shaped by the metabolic network under certain environmental circumstances (46). Trans-editing proteins such as ProXp-ST1 and ProXp-ST2 clearly fit into this category, with the ability to act on multiple aa-tRNA substrates depending on the pressures experienced by the cellular translational machinery.…”

Section: Discussionmentioning

confidence: 99%

Homologous trans -editing factors with broad tRNA specificity prevent mistranslation caused by serine/threonine misactivation

Liu

Vargas-Rodriguez

Goto

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Aminoacyl-tRNA synthetases (ARSs) establish the rules of the genetic code, whereby each amino acid is attached to a cognate tRNA. Errors in this process lead to mistranslation, which can be toxic to cells. The selective forces exerted by species-specific requirements and environmental conditions potentially shape qualitycontrol mechanisms that serve to prevent mistranslation. A family of editing factors that are homologous to the editing domain of bacterial prolyl-tRNA synthetase includes the previously characterized trans-editing factors ProXp-ala and YbaK, which clear Ala-tRNA Pro and Cys-tRNA Pro , respectively, and three additional homologs of unknown function, ProXp-x, ProXp-y, and ProXp-z. We performed an in vivo screen of 230 conditions in which an Escherichia coli proXp-y deletion strain was grown in the presence of elevated levels of amino acids and specific ARSs. This screen, together with the results of in vitro deacylation assays, revealed Ser-and Thr-tRNA deacylase function for this homolog. A similar activity was demonstrated for Bordetella parapertussis ProXp-z in vitro. These proteins, now renamed "ProXp-ST1" and "ProXp-ST2," respectively, recognize multiple tRNAs as substrates. Taken together, our data suggest that these free-standing editing domains have the ability to prevent mistranslation errors caused by a number of ARSs, including lysyl-tRNA synthetase, threonyl-tRNA synthetase, seryl-tRNA synthetase, and alanyl-tRNA synthetase. The expression of these multifunctional enzymes is likely to provide a selective growth advantage to organisms subjected to environmental stresses and other conditions that alter the amino acid pool.aminoacyl tRNA synthetase | protein synthesis | ProXp | quality control | trans-editing

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“…If this is not the case, the incidence of exaptation may be reduced. In this regard, we note that 84 percent of E. coli transporters can transport multiple molecules 17 , and that their substrate specificity can change rapidly 18 , thus ameliorating this constraint. Fourth, real metabolic networks may contain more reactions connected to the rest of metabolism than our randomly sampled networks.…”

mentioning

confidence: 94%

“…The abundance of non-adaptive trait origins results from the complexity of metabolic systems, which have many enzyme parts that can jointly form multiple metabolic phenotypes, but this ability is not restricted to metabolic networks. Many enzymes are capable of utilizing various substrates 17,19 , which can further increase network complexity and the potential for exaptation. The ability to form multiple phenotypes also occurs in regulatory circuits 20 , which can form different molecular activity patterns, as well as RNA molecules 21 , which can form multiple conformations with different biological functions.…”

mentioning

confidence: 99%

A latent capacity for evolutionary innovation through exaptation in metabolic systems

Barve

Wagner

2013

Nature

135

136

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Some evolutionary innovations may originate non-adaptively as exaptations, or pre-adaptations, which are by-products of other adaptive traits. Examples include feathers, which originated before they were used in flight, and lens crystallins, which are light-refracting proteins that originated as enzymes. The question of how often adaptive traits have non-adaptive origins has profound implications for evolutionary biology, but is difficult to address systematically. Here we consider this issue in metabolism, one of the most ancient biological systems that is central to all life. We analyse a metabolic trait of great adaptive importance: the ability of a metabolic reaction network to synthesize all biomass from a single source of carbon and energy. We use novel computational methods to sample randomly many metabolic networks that can sustain life on any given carbon source but contain an otherwise random set of known biochemical reactions. We show that when we require such networks to be viable on one particular carbon source, they are typically also viable on multiple other carbon sources that were not targets of selection. For example, viability on glucose may entail viability on up to 44 other sole carbon sources. Any one adaptation in these metabolic systems typically entails multiple potential exaptations. Metabolic systems thus contain a latent potential for evolutionary innovations with non-adaptive origins. Our observations suggest that many more metabolic traits may have non-adaptive origins than is appreciated at present. They also challenge our ability to distinguish adaptive from non-adaptive traits. include feathers, which originated before they adopted a role in flight 2 , and lens crystallins, light-refracting proteins that originated as enzymes 6 . The incidence of non-adaptive trait origins has profound implications for evolutionary biology, but it has thus far not been possible to study this incidence systematically. We here study it in metabolism, one of the most ancient biological systems that is central to all life. We analyse metabolic traits of great adaptive importance, the ability of a metabolic reaction network to synthesize all biomass from a single (sole) source of carbon and energy. We take advantage of novel computational methods to randomly sample many metabolic networks that can sustain life on any given carbon source, but that contain an otherwise random set of known biochemical reactions. We show that such random networks, required to be viable on one carbon source C, are typically also viable on multiple other carbon sources C new that were not targets of selection. For example, viability on glucose may entail viability on up to 44 other sole carbon sources. Any one adaptation in these metabolic systems typically entails multiple potential exaptations.Metabolic systems thus contain a latent potential for evolutionary innovations with non-adaptive origins. Our observations suggest that many more metabolic traits than currently appreciated may have non-adaptive origins. T...

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Network Context and Selection in the Evolution to Enzyme Specificity

Cited by 258 publications

References 75 publications

Biophysics of protein evolution and evolutionary protein biophysics

Biophysics of protein evolution and evolutionary protein biophysics

Homologous trans -editing factors with broad tRNA specificity prevent mistranslation caused by serine/threonine misactivation

A latent capacity for evolutionary innovation through exaptation in metabolic systems

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