Rapid bursts and slow declines: on the possible evolutionary trajectories of enzymes

Newton, Matilda; Arcus, Vickery L.; Patrick, Wayne M.

doi:10.1098/rsif.2015.0036

Cited by 26 publications

(29 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In most likelihood, the traits of natural proteins were shaped in response to most relevant environment, that is, under the most demanding conditions with respect to a given protein. These conditions may relate to the distant past and are largely unknown, and would thus be extremely difficult to reproduced in the laboratory. Regardless of its origins, buffering results in “robustness” to mutations—namely, mutations show no experimentally measureable effects on organismal phenotype unless they drastically decrease the protein's functional output.…”

Section: Buffering the Effects Of Mutationsmentioning

confidence: 99%

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature

2016

View full text Add to dashboard Cite

The last decade has seen a growing number of experiments aimed at systematically mapping the effects of mutations in different proteins, and of attempting to correlate their biophysical and biochemical effects with organismal fitness. While insightful, systematic laboratory measurements of fitness effects present challenges and difficulties. Here, we discuss the limitations associated with such measurements, and in particular the challenge of correlating the effects of mutations at the single protein level ("protein fitness") with their effects on organismal fitness. A variety of experimental setups are used, with some measuring the direct effects on protein function and others monitoring the growth rate of a model organism carrying the protein mutants. The manners by which fitness effects are calculated and presented also vary, and the conclusions, including the derived distributions of fitness effects of mutations, vary accordingly. The comparison of the effects of mutations in the laboratory to the natural protein diversity, namely to amino acid changes that have fixed in the course of millions of years of evolution, is also debatable. The results of laboratory experiments may, therefore, be less relevant to understanding long-term inter-species variations yet insightful with regard to short-term polymorphism, for example, in the study of the effects of human SNPs.

show abstract

Section: Buffering the Effects Of Mutationsmentioning

confidence: 99%

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature

2016

View full text Add to dashboard Cite

show abstract

“…Several evolutionary forces lead to the accumulation of functions in genomic repertoires, including HGT, gene rearrangements, and gene duplications [8, 14, 26]. These events shape and increase genomic abundance and corresponding molecular functions [8, 42, 47].…”

Section: Resultsmentioning

confidence: 99%

The natural history of molecular functions inferred from an extensive phylogenomic analysis of gene ontology data

Koç

Caetano‐Anollés

2017

PLoS ONE

View full text Add to dashboard Cite

The origin and natural history of molecular functions hold the key to the emergence of cellular organization and modern biochemistry. Here we use a genomic census of Gene Ontology (GO) terms to reconstruct phylogenies at the three highest (1, 2 and 3) and the lowest (terminal) levels of the hierarchy of molecular functions, which reflect the broadest and the most specific GO definitions, respectively. These phylogenies define evolutionary timelines of functional innovation. We analyzed 249 free-living organisms comprising the three superkingdoms of life, Archaea, Bacteria, and Eukarya. Phylogenies indicate catalytic, binding and transport functions were the oldest, suggesting a ‘metabolism-first’ origin scenario for biochemistry. Metabolism made use of increasingly complicated organic chemistry. Primordial features of ancient molecular functions and functional recruitments were further distilled by studying the oldest child terms of the oldest level 1 GO definitions. Network analyses showed the existence of an hourglass pattern of enzyme recruitment in the molecular functions of the directed acyclic graph of molecular functions. Older high-level molecular functions were thoroughly recruited at younger lower levels, while very young high-level functions were used throughout the timeline. This pattern repeated in every one of the three mappings, which gave a criss-cross pattern. The timelines and their mappings were remarkable. They revealed the progressive evolutionary development of functional toolkits, starting with the early rise of metabolic activities, followed chronologically by the rise of macromolecular biosynthesis, the establishment of controlled interactions with the environment and self, adaptation to oxygen, and enzyme coordinated regulation, and ending with the rise of structural and cellular complexity. This historical account holds important clues for dissection of the emergence of biomcomplexity and life.

show abstract

“…Even if this artificially increased expression by 1-2 orders of magnitude (making our HisA variants among the most highly expressed metabolic enzymes in each strain), the total intracellular TrpF activities of the evolved S. enterica strains would still be lower than those of E. coli and M. tuberculosis. Thus, some bacteria may have TrpF enzymes that exceed their performance thresholds and have "excess capacity" at this node in the metabolic network (27).…”

Section: Discussionmentioning

confidence: 99%

Structural and functional innovations in the real-time evolution of new (βα) ₈ barrel enzymes

Newton

Guo

Söderholm

et al. 2017

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

Self Cite

107

View full text Add to dashboard Cite

New genes can arise by duplication and divergence, but there is a fundamental gap in our understanding of the relationship between these genes, the evolving proteins they encode, and the fitness of the organism. Here we used crystallography, NMR dynamics, kinetics, and mass spectrometry to explain the molecular innovations that arose during a previous real-time evolution experiment. In that experiment, the (βα) 8 barrel enzyme HisA was under selection for two functions (HisA and TrpF), resulting in duplication and divergence of the hisA gene to encode TrpF specialists, HisA specialists, and bifunctional generalists. We found that selection affects enzyme structure and dynamics, and thus substrate preference, simultaneously and sequentially. Bifunctionality is associated with two distinct sets of loop conformations, each essential for one function. We observed two mechanisms for functional specialization: structural stabilization of each loop conformation and substrate-specific adaptation of the active site. Intracellular enzyme performance, calculated as the product of catalytic efficiency and relative expression level, was not linearly related to fitness. Instead, we observed thresholds for each activity above which further improvements in catalytic efficiency had little if any effect on growth rate. Overall, we have shown how beneficial substitutions selected during real-time evolution can lead to manifold changes in enzyme function and bacterial fitness. This work emphasizes the speed at which adaptive evolution can yield enzymes with sufficiently high activities such that they no longer limit the growth of their host organism, and confirms the (βα) 8 barrel as an inherently evolvable protein scaffold.HisA | TrpF | adaptive evolution | enzyme performance threshold

show abstract

Rapid bursts and slow declines: on the possible evolutionary trajectories of enzymes

Cited by 26 publications

References 85 publications

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature

The natural history of molecular functions inferred from an extensive phylogenomic analysis of gene ontology data

Structural and functional innovations in the real-time evolution of new (βα) ₈ barrel enzymes

Contact Info

Product

Resources

About

Rapid bursts and slow declines: on the possible evolutionary trajectories of enzymes

Cited by 26 publications

References 85 publications

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature

Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature

The natural history of molecular functions inferred from an extensive phylogenomic analysis of gene ontology data

Structural and functional innovations in the real-time evolution of new (βα) 8 barrel enzymes

Contact Info

Product

Resources

About

Structural and functional innovations in the real-time evolution of new (βα) ₈ barrel enzymes