Compensatory mutations are repeatable and clustered within proteins

Davis, Brian; Poon, Art F. Y.; Whitlock, Michael C.

doi:10.1098/rspb.2008.1846

Cited by 63 publications

(53 citation statements)

References 26 publications

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“…A high density of interactions has also been reported in a survey of published data on suppressor mutations in viruses, prokaryotes and eukaryotes Davis et al 2009). In some cases suppressor mutations recover fitness in individuals with a deleterious mutation by suppressing the phenotypic effect of the deleterious mutation and are therefore compensatory.…”

Section: Discussionmentioning

confidence: 99%

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

et al. 2010

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Fitness epistasis, the interaction among alleles at different loci in their effects on fitness, has potentially important consequences for adaptive evolution. We investigated fitness epistasis among amino acids of a functionally important region of the human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein (gp120). Seven mutations putatively involved in the adaptation of the second conserved to third variable protein region (C2-V3) to the use of an alternative host-cell chemokine coreceptor (CXCR4) for cell entry were engineered singly and in combinations on the wild-type genetic background and their effects on viral infectivity were measured. Epistasis was found to be common and complex, involving not only pairwise interactions, but also higher-order interactions. Interactions could also be surprisingly strong, changing fitness by more than 9 orders of magnitude, which is explained by some single mutations being practically lethal. A consequence of the observed epistasis is that many of the minimum-length mutational trajectories between the wild type and the mutant with highest fitness on cells expressing the alternative coreceptor are selectively inaccessible. These results may help explain the difficulty of evolving viruses that use the alternative coreceptor in culture and the delayed evolution of this phenotype in natural infection. Knowledge of common, complex, and strong fitness interactions among amino acids is necessary for a full understanding of protein evolution.

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Section: Discussionmentioning

confidence: 99%

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

et al. 2010

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“…Instead, they are almost always accompanied by other mutations of smaller effect, located farther from the functional site 100 . These ‘secondary’ mutations typically do not occur in parallel but instead affect different sites and/or states among lineages, even when the large-effect mutations are parallel 32,89,90,93,101 .…”

Section: Insights From Evolutionary Biochemistrymentioning

confidence: 99%

Evolutionary biochemistry: revealing the historical and physical causes of protein properties

2013

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The repertoire of proteins and nucleic acids in the living world is determined by evolution; their properties are determined by the laws of physics and chemistry. Explanations of these two kinds of causality — the purviews of evolutionary biology and biochemistry, respectively — are typically pursued in isolation, but many fundamental questions fall squarely at the interface of fields. Here we articulate the paradigm of evolutionary biochemistry, which aims to dissect the physical mechanisms and evolutionary processes by which biological molecules diversified and to reveal how their physical architecture facilitates and constrains their evolution. We show how an integration of evolution with biochemistry moves us towards a more complete understanding of why biological molecules have the properties that they do.

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“…Reverse evolution experiments also show that ancestral fitness values can be recovered given sufficient evolution time [60]. In addition, compensatory mutations occur more often than back mutations [10], indicating the existence of multiple evolutionary trajectories. These results are consistent with OptiEvo theory predictions (a) and (c).…”

Section: Predictions and Empirical Assessments Of Optievo Theory In Nmentioning

confidence: 95%

Fundamental Principles of Control Landscapes with Applications to Quantum Mechanics, Chemistry and Evolution

Rabitz

et al. 2014

Recent Advances in the Theory and Application of Fitness Landscapes

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Abstract. The concept of a landscape or response surface naturally arises in applications widely ranging over the sciences, engineering and other disciplines. A landscape is the desired output as a function of a set of input variables, often of very high dimension. The relationship between the features of a landscape and the input variables is usually unknown a priori and often thought to be highly complex due to the anticipated intricate interactions involved. This chapter reviews recent developments in the analysis of landscape topology with the input variables considered as controls. Taking a control perspective allows for the specification of particular assumptions whose satisfaction permits a general analysis of the landscape topology. Satisfaction of these conditions leads to the conclusion that control landscapes should be devoid of suboptimal critical point traps, thereby permitting ready excursions without hindrance to the highest values of the landscape. These principles are set out in a general framework and then specifically illustrated for applications

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Compensatory mutations are repeatable and clustered within proteins

Cited by 63 publications

References 26 publications

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region

Evolutionary biochemistry: revealing the historical and physical causes of protein properties

Fundamental Principles of Control Landscapes with Applications to Quantum Mechanics, Chemistry and Evolution

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