Multidimensional epistasis and fitness landscapes in enzyme evolution

2012 ◽  
Vol 445 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Wei Zhang ◽  
Daniel F. A. R. Dourado ◽  
Pedro Alexandrino Fernandes ◽  
Maria João Ramos ◽  
Bengt Mannervik
Keyword(s):  
Glutathione Transferase ◽  
Fitness Landscape ◽  
Evolutionary Process ◽  
Salient Feature ◽  
Selective Advantage ◽  
Enzyme Evolution ◽  
Conventional Analysis ◽  
Evolutionary Response ◽  
Single Protein ◽  
Evolutionary Trajectories

The conventional analysis of enzyme evolution is to regard one single salient feature as a measure of fitness, expressed in a milieu exposing the possible selective advantage at a given time and location. Given that a single protein may serve more than one function, fitness should be assessed in several dimensions. In the present study we have explored individual mutational steps leading to a triple-point-mutated human GST (glutathione transferase) A2-2 displaying enhanced activity with azathioprine. A total of eight alternative substrates were used to monitor the diverse evolutionary trajectories. The epistatic effects of the mutations on catalytic activity were variable in sign and magnitude and depended on the substrate used, showing that epistasis is a multidimensional quality. Evidently, the multidimensional fitness landscape can lead to alternative trajectories resulting in enzymes optimized for features other than the selectable markers relevant at the origin of the evolutionary process. In this manner the evolutionary response is robust and can adapt to changing environmental conditions.

scholarly journals Criticality in tumor evolution and clinical outcome

2018 ◽  
Vol 115 (47) ◽  
pp. E11101-E11110 ◽  
Author(s):  
Erez Persi ◽  
Yuri I. Wolf ◽  
Mark D. M. Leiserson ◽  
Eugene V. Koonin ◽  
Eytan Ruppin
Keyword(s):  
Clinical Outcome ◽  
Cancer Biology ◽  
Patient Survival ◽  
Fitness Landscape ◽  
Purifying Selection ◽  
Nonlinear Effects ◽  
Tumor Evolution ◽  
Evolutionary Trajectories ◽  
Cancer Types ◽  
Selection Phase

How mutation and selection determine the fitness landscape of tumors and hence clinical outcome is an open fundamental question in cancer biology, crucial for the assessment of therapeutic strategies and resistance to treatment. Here we explore the mutation-selection phase diagram of 6,721 tumors representing 23 cancer types by quantifying the overall somatic point mutation load (ML) and selection (dN/dS) in the entire proteome of each tumor. We show that ML strongly correlates with patient survival, revealing two opposing regimes around a critical point. In low-ML cancers, a high number of mutations indicates poor prognosis, whereas high-ML cancers show the opposite trend, presumably due to mutational meltdown. Although the majority of cancers evolve near neutrality, deviations are observed at extreme MLs. Melanoma, with the highest ML, evolves under purifying selection, whereas in low-ML cancers, signatures of positive selection are observed, demonstrating how selection affects tumor fitness. Moreover, different cancers occupy specific positions on the ML–dN/dS plane, revealing a diversity of evolutionary trajectories. These results support and expand the theory of tumor evolution and its nonlinear effects on survival.

scholarly journals Biological evolution — a semiotically constrained growth of complexity

2002 ◽  
Vol 30 (1) ◽  
pp. 271-282
Author(s):  
Abir U. Igamberdiev
Keyword(s):  
Golden Ratio ◽  
Biological Evolution ◽  
Evolutionary Process ◽  
Generative Grammar ◽  
Selective Advantage ◽  
Living System ◽  
The State ◽  
Final Cause ◽  
Reflective Process ◽  
Time Future

Any living system possesses internal embedded description and exists as a superposition of different potential realisations, which are reduced in interaction with the environment. This reduction cannot be recursively deduced from the state in time present, it includes unpredictable choice and needs to be modelled also from the state in time future. Such non-recursive establishment of emerging configuration, after its memorisation via formation of reflective loop (sign-creating activity), becomes the inherited recursive action. It leads to increase of complexity of the embedded description, which constitutes the rules of generative grammar defining possible directions of open evolutionary process. The states in time future can be estimated from the point of their perfection, which represents the final cause in the Aristotelian sense and may possess a selective advantage. The limits of unfolding of the reflective process, such as the golden ratio and the golden wurf are considered as the canons of perfection established in the evolutionary process.

scholarly journals Adaptive fitness landscape for replicator systems: to maximize or not to maximize

2018 ◽  
Vol 13 (3) ◽  
pp. 25 ◽  
Author(s):  
Alexander S. Bratus ◽  
Yuri S. Semenov ◽  
Artem S. Novozhilov
Keyword(s):  
Natural Selection ◽  
Fitness Landscape ◽  
Evolutionary Process ◽  
Hill Climbing ◽  
Adaptive Landscape ◽  
Basic Model ◽  
Mean Fitness ◽  
The Mean ◽  
The Hill ◽  
Fisher’S Fundamental Theorem

Sewall Wright’s adaptive landscape metaphor penetrates a significant part of evolutionary thinking. Supplemented with Fisher’s fundamental theorem of natural selection and Kimura’s maximum principle, it provides a unifying and intuitive representation of the evolutionary process under the influence of natural selection as the hill climbing on the surface of mean population fitness. On the other hand, it is also well known that for many more or less realistic mathematical models this picture is a severe misrepresentation of what actually occurs. Therefore, we are faced with two questions. First, it is important to identify the cases in which adaptive landscape metaphor actually holds exactly in the models, that is, to identify the conditions under which system’s dynamics coincides with the process of searching for a (local) fitness maximum. Second, even if the mean fitness is not maximized in the process of evolution, it is still important to understand the structure of the mean fitness manifold and see the implications of this structure on the system’s dynamics. Using as a basic model the classical replicator equation, in this note we attempt to answer these two questions and illustrate our results with simple well studied systems.

scholarly journals Ribosome Dimerization Protects the Small Subunit

2020 ◽  
Vol 202 (10) ◽  
Author(s):  
Heather A. Feaga ◽  
Mykhailo Kopylov ◽  
Jenny Kim Kim ◽  
Marko Jovanovic ◽  
Jonathan Dworkin
Keyword(s):  
Ribosomal Proteins ◽  
Selective Advantage ◽  
Small Subunit ◽  
Content Type ◽  
Dimer Interface ◽  
Cryo Electron Microscopy ◽  
Single Protein ◽  
Mechanistic Basis ◽  
Favorable Conditions ◽  
Insight Into

ABSTRACT When nutrients become scarce, bacteria can enter an extended state of quiescence. A major challenge of this state is how to preserve ribosomes for the return to favorable conditions. Here, we show that the ribosome dimerization protein hibernation-promoting factor (HPF) functions to protect essential ribosomal proteins. Ribosomes isolated from strains lacking HPF (Δhpf) or encoding a mutant allele of HPF that binds the ribosome but does not mediate dimerization were substantially depleted of the small subunit proteins S2 and S3. Strikingly, these proteins are located directly at the ribosome dimer interface. We used single-particle cryo-electron microscopy (cryo-EM) to further characterize these ribosomes and observed that a high percentage of ribosomes were missing S2, S3, or both. These data support a model in which the ribosome dimerization activity of HPF evolved to protect labile proteins that are essential for ribosome function. HPF is almost universally conserved in bacteria, and HPF deletions in diverse species exhibit decreased viability during starvation. Our data provide mechanistic insight into this phenotype and establish a mechanism for how HPF protects ribosomes during quiescence. IMPORTANCE The formation of ribosome dimers during periods of dormancy is widespread among bacteria. Dimerization is typically mediated by a single protein, hibernation-promoting factor (HPF). Bacteria lacking HPF exhibit strong defects in viability and pathogenesis and, in some species, extreme loss of rRNA. The mechanistic basis of these phenotypes has not been determined. Here, we report that HPF from the Gram-positive bacterium Bacillus subtilis preserves ribosomes by preventing the loss of essential ribosomal proteins at the dimer interface. This protection may explain phenotypes associated with the loss of HPF, since ribosome protection would aid survival during nutrient limitation and impart a strong selective advantage when the bacterial cell rapidly reinitiates growth in the presence of sufficient nutrients.

Escalation in Late Cretaceous-early Paleocene oysters (Gryphaeidae) from the Atlantic Coastal Plain

Paleobiology ◽  
2000 ◽  
Vol 26 (2) ◽  
pp. 215-237 ◽  
Author(s):  
Gregory P. Dietl ◽  
Richard R. Alexander ◽  
Walter F. Bien
Keyword(s):  
Late Cretaceous ◽  
Coastal Plain ◽  
Selective Advantage ◽  
Atlantic Coastal Plain ◽  
Independent Evidence ◽  
Evolutionary Response ◽  
Frequency Independent ◽  
Early Paleocene ◽  
Surface Ornamentation ◽  
Atlantic Coastal

More than 1600 valves of Late Cretaceous and early Paleocene Northern Atlantic Coastal Plain gryphaeid oysters (Exogyrinae and Pycnodonteinae) were examined for breakage-induced shell repair and morphologic variability to evaluate the hypothesis of escalation. The Exogyrinae show disproportionately higher average repair frequency (0.41) relative to the ecologically and functionally similar unornamented pycnodonts (0.19). An increase in repair frequency (independent evidence of the action of a selective agent, e.g., predation) through the stratigraphic interval supports escalation. Variation in repair frequencies may reflect differences in oyster morphology and in the strength and diversity of shell crushers across an onshore-offshore gradient. Escalation of antipredatory adaptation characterized the evolutionary response of gryphaeid oysters to their durophagous predators. Adaptation generally occurred by the enhancement of existing traits in both oyster lineages. Characters that confer a selective advantage against predators are not all expressed or improved concurrently in both oyster lineages. Morphologic adaptations to minimize shell breakage include the development of expansive, broad commissural shelves, thickened valves, and surface ornamentation (Exogyrinae). Surface ornament in the Exogyrinae gradually increased with time. For some characters, such as thickness, conflicting functional demands (e.g., valve stabilization) may have limited adaptation to predators.

Multi-substrate–activity space and quasi-species in enzyme evolution: Ohno's dilemma, promiscuity and functional orthogonality

2009 ◽  
Vol 37 (4) ◽  
pp. 740-744 ◽  
Author(s):  
Bengt Mannervik ◽  
Arna Runarsdottir ◽  
Sanela Kurtovic
Keyword(s):  
Multivariate Analysis ◽  
Directed Evolution ◽  
Enzyme Evolution ◽  
Activity Space ◽  
Glutathione Transferases ◽  
Multidimensional Space ◽  
Alternative Substrates ◽  
Catalytic Activities ◽  
Evolutionary Trajectories

A functional enzyme displays activity with at least one substrate and can be represented by a vector in substrate–activity space. Many enzymes, including GSTs (glutathione transferases), are promiscuous in the sense that they act on alternative substrates, and the corresponding vectors operate in multidimensional space. The direction of the vector is governed by the relative activities of the diverse substrates. Stochastic mutations of already existing enzymes generate populations of variants, and clusters of functionally similar mutants can serve as parents for subsequent generations of enzymes. The proper evolving unit is a functional quasi-species, which may not be identical with the ‘best’ variant in its generation. The manifestation of the quasi-species is dependent on the substrate matrix used to explore catalytic activities. Multivariate analysis is an approach to identifying quasi-species and to investigate evolutionary trajectories in the directed evolution of enzymes for novel functions.

Constructing and Analyzing the Fitness Landscape of an Experimental Evolutionary Process

ChemBioChem ◽  
2008 ◽  
Vol 9 (14) ◽  
pp. 2260-2267 ◽  
Author(s):  
Manfred T. Reetz ◽  
Joaquin Sanchis
Keyword(s):  
Fitness Landscape ◽  
Evolutionary Process

scholarly journals Mortality and coexistence time both cause changes in predator-prey co-evolutionary dynamics

2020 ◽  
Author(s):  
Thomas Scheuerl ◽  
Veijo Kaitala
Keyword(s):  
Evolutionary Dynamics ◽  
Evolutionary Process ◽  
Mortality Rates ◽  
Predator Prey ◽  
Ecological Changes ◽  
Evolutionary Changes ◽  
Predation Efficiency ◽  
Evolutionary Trajectories ◽  
Predator Defence ◽  
Transfer Interval

AbstractAll organisms are sensitive to the abiotic environment, and in multispecies communities a deteriorating environment increasing mortality and limiting coexistence time can cause ecological changes. When interaction within the community is changed this can impact co-evolutionary processes. Here we use a mathematical model to predict ecological and evolutionary changes in a simple predator-prey community under different mortality rates and times of coexistence, both controlled by various transfer volume and transfer interval. In the simulated bacteria-ciliate system, we find species densities to be surprisingly robust under changed mortality rates and times both species coexist, resulting in stable densities. Confirming a theoretical prediction however, the evolution of anti-predator defence in the bacteria and evolution of predation efficiency in ciliates relax under high mortalities and limited times both partners interact. In contrast, evolutionary trajectories intensify when global mortalities are low, and the predator-prey community has more time for close interaction. These results provide testable hypotheses for future studies of predator-prey systems and we hope this work will help to bridge the gap in our knowledge how ecological and evolutionary process together shape composition of microbial communities.

scholarly journals The roles of standing genetic variation and evolutionary history in determining the evolvability of anti-predator strategies

2014 ◽  
Author(s):  
Jordan Fish ◽  
Daniel R O'Donnell ◽  
Abhijna Parigi ◽  
Ian Dworkin ◽  
Aaron P Wagner
Keyword(s):  
Genetic Variation ◽  
Evolutionary History ◽  
Relative Importance ◽  
Digital Evolution ◽  
Relative Ease ◽  
Evolutionary Response ◽  
Two Factors ◽  
The Face ◽  
Evolutionary Trajectories ◽  
Different Levels

Standing genetic variation and the historical environment in which that variation arises (evolutionary history) are both potentially significant determinants of a population’s capacity for evolutionary response to a changing environment. We evaluated the relative importance of these two factors in influencing the evolutionary trajectories in the face of sudden environmental change. We used the open-ended digital evolution software Avida to examine how historic exposure to predation pressures, different levels of genetic variation, and combinations of the two, impact anti-predator strategies and competitive abilities evolved in the face of threats from new, invasive, predator populations. We show that while standing genetic variation plays some role in determining evolutionary responses, evolutionary history has the greater influence on a population’s capacity to evolve effective anti-predator traits. This adaptability likely reflects the relative ease of repurposing existing, relevant genes and traits, and the broader potential value of the generation and maintenance of adaptively flexible traits in evolving populations.

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