The Evolution of Epistasis and Its Links With Genetic Robustness, Complexity and Drift in a Phenotypic Model of Adaptation

Gros, Pierre-Alexis; Nagard, Hervé Le; Tenaillon, Olivier

doi:10.1534/genetics.108.099127

Cited by 94 publications

(110 citation statements)

References 68 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…For this comparison we analyzed the relationship between s and ε for previous datasets from M. extorquens and E. coli where the beneficial mutations occurred consecutively in a variety of genes across the genome of a single adapting lineage [10], [11], combinations of mutations from two genes of the bacteriophage ID11 [12], and two datasets of within-protein interactions for β-lactamase [17], [38]. These datasets also displayed signs of a correlation between s and increasingly negative ε (as noted in [37]), with the exception of the intragenic data for β-lactamase (Figure S1). …”

Section: Resultsmentioning

confidence: 97%

Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations

et al. 2014

View full text Add to dashboard Cite

How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncover the fitness landscape defined by gene expression levels. We found strong antagonism and sign epistasis between these beneficial mutations. Mutations with the largest individual benefit interacted the most antagonistically with other mutations, a trend we also uncovered through analyses of datasets from other model systems. However, these beneficial mutations interacted multiplicatively (i.e., no epistasis) at the level of enzyme expression. By generating a model that predicts fitness from enzyme levels we could explain the observed sign epistasis as a result of overshooting the optimum defined by a balance between enzyme catalysis benefits and fitness costs. Knowledge of the phenotypic landscape also illuminated that, although the fitness peak was phenotypically far from the ancestral state, it was not genetically distant. Single beneficial mutations jumped straight toward the global optimum rather than being constrained to change the expression phenotypes in the correlated fashion expected by the genetic architecture. Given that adaptation in nature often results from optimizing gene expression, these conclusions can be widely applicable to other organisms and selective conditions. Poor interactions between individually beneficial alleles affecting gene expression may thus compromise the benefit of sex during adaptation and promote genetic differentiation.

show abstract

Section: Resultsmentioning

confidence: 97%

Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Finally, epistasis (Q) can also influence drift intensity. Larger values of Q (.2) imply more negative epistasis between pairs of mutations (Gros et al 2009) and thus increase selection intensity: deleterious mutations have smaller probabilities of becoming fixed when epistasis is more negative. It is hence not a surprise to find that drift intensity is inversely related to Q.…”

Section: Discussionmentioning

confidence: 99%

“…The parameter Q , set to 2 in classical quantitative genetics, defines the sign of average epistasis among pair of mutations: null when Q ¼ 2 (Martin et al 2007) and positive (negative) if it is smaller (larger) than 2 (Gros et al 2009). Q affects the sharpness of the transition from high to low fitness value around the distance R 1/Q that always has fitness equal to $ 1 3 C(R) (Figure 2).…”

Section: Modelmentioning

confidence: 99%

Selection for Chaperone-Like Mediated Genetic Robustness at Low Mutation Rate: Impact of Drift, Epistasis and Complexity

Gros

Tenaillon

2009

Genetics

Self Cite

View full text Add to dashboard Cite

Genetic robustness is defined as the constancy of a phenotype in the face of deleterious mutations. Overexpression of chaperones, to assist the folding of proteins carrying deleterious mutations, is so far one of the most accepted molecular mechanisms enhancing genetic robustness. Most theories on the evolution of robustness have focused on the implications of high mutation rate. Here we show that genetic drift, which is modulated by population size, organism complexity, and epistasis, can be a sufficient force to select for chaperone-mediated genetic robustness. Using an exact analytical solution, we also show that selection for costly genetic robustness leads to a paradox: the decrease of population fitness on long timescales and the long-term dependency on robustness mechanisms. We suggest that selection for genetic robustness could be universal and not restricted to high mutation rate organisms such as RNA viruses. The evolution of the endosymbiont Buchnera illustrates this selection mechanism and its paradox: the increased dependency on chaperones mediating genetic robustness. Our model explains why most chaperones might have become essential even in optimal growth conditions.

show abstract

“…Pleiotropy could provide such a buffering mechanism if multiple genes contribute pleiotropically to a trait rather than a single gene targeted solely to that trait, because the functioning of the trait would not be entirely dependent on the activity of a single gene. Robustness is itself related to the curvature of the fitness function, with concave fitness curves yielding higher robustness to stochastic noise (Gros et al 2009). Nevertheless, the connection between robustness and the evolution of pleiotropy has yet to be explored explicitly.…”

Section: Evolution Of Pleiotropy 1391mentioning

confidence: 99%

Gene Functional Trade-Offs and the Evolution of Pleiotropy

Guillaume¹,

Otto

2012

Genetics

View full text Add to dashboard Cite

Pleiotropy is the property of genes affecting multiple functions or characters of an organism. Genes vary widely in their degree of pleiotropy, but this variation is often considered a by-product of their evolutionary history. We present a functional theory of how pleiotropy may itself evolve. We consider genes that contribute to two functions, where contributing more to one function detracts from allocation to the second function. We show that whether genes become pleiotropic or specialize on a single function depends on the nature of trade-offs as gene activities contribute to different traits and on how the functionality of these traits affects fitness. In general, when a gene product can perform well at two functions, it evolves to do so, but not when pleiotropy would greatly disrupt each function. Consequently, reduced pleiotropy should often evolve, with genes specializing on the trait that is currently more important to fitness. Even when pleiotropy does evolve, not all genes are expected to become equally pleiotropic; genes with higher levels of expression are more likely to evolve greater pleiotropy. For the case of gene duplicates, we find that perfect subfunctionalization evolves only under stringent conditions. More often, duplicates are expected to maintain a certain degree of functional redundancy, with the gene contributing more to trait functionality evolving the highest degree of pleiotropy. Gene product interactions can facilitate subfunctionalization, but whether they do so depends on the curvature of the fitness surface. Finally, we find that stochastic gene expression favors pleiotropy by selecting for robustness in fitness components. PLEIOTROPY is the property whereby a gene affects more than one function or phenotypic character of an organism. Gene-knockout studies in yeast indicate that deleting genes with higher degrees of pleiotropy has, on average, a more harmful effect on fitness (Salathé et al. 2006; Cooper et al. 2007). This negative relationship with fitness is expected given that most mutational changes are deleterious so that the more characters are affected by a mutation, the more likely the net effect on fitness is harmful, even if the mutation is beneficial for a subset of characters. This claim has been verified in theoretical studies based on Fisher's geometrical model (Chevin et al. 2010;Lourenço et al. 2011). Pleiotropy is consequently seen as a constraint on evolution because it reduces the adaptive capacity of an organism (Orr 2000;Welch and Waxman 2003).Recent observations in a variety of species have found that the extent of pleiotropy varies among genes and is often limited, with a majority of genes influencing a small set of traits while a few genes affect many traits (Dudley et al. 2005; Albert et al. 2008;Wagner et al. 2008;Wang et al. 2010;Wagner and Zhang 2011). This is in direct opposition to the historical assumption of universal pleiotropy underlying most population and quantitative genetics approaches to the joint evolution of multiple characters (...

show abstract

The Evolution of Epistasis and Its Links With Genetic Robustness, Complexity and Drift in a Phenotypic Model of Adaptation

Cited by 94 publications

References 68 publications

Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations

Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations

Selection for Chaperone-Like Mediated Genetic Robustness at Low Mutation Rate: Impact of Drift, Epistasis and Complexity

Gene Functional Trade-Offs and the Evolution of Pleiotropy

Contact Info

Product

Resources

About