The evolutionary context of robust and redundant cell biological mechanisms

Delattre, Marie; Félix, Marie‐Anne

doi:10.1002/bies.200800215

Cited by 15 publications

(10 citation statements)

References 64 publications

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“…Redundancy of elements acting in a given system, such as genes, transcriptional enhancers, pathways or cells, tends to make systems resilient to genetic or environmental perturbations [85][86][87][88][89][90] . It is usually unclear whether redundancy is maintained in evolution because of redundancy per se or because of the pleiotropic effects of the elements showing redundancy.…”

Section: Nonlinearity In Multiple Genes To Phenotype Mappingmentioning

confidence: 99%

Pervasive robustness in biological systems

Félix¹,

Barkoulas²

2015

Nat Rev Genet

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Robustness is characterized by the invariant expression of a phenotype in the face of a genetic and/or environmental perturbation. Although phenotypic variance is a central measure in the mapping of the genotype and environment to the phenotype in quantitative evolutionary genetics, robustness is also a key feature in systems biology, resulting from nonlinearities in quantitative relationships between upstream and downstream components. In this Review, we provide a synthesis of these two lines of investigation, converging on understanding how variation propagates across biological systems. We critically assess the recent proliferation of studies identifying robustness-conferring genes in the context of the nonlinearity in biological systems.

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Section: Nonlinearity In Multiple Genes To Phenotype Mappingmentioning

confidence: 99%

Pervasive robustness in biological systems

Félix¹,

Barkoulas²

2015

Nat Rev Genet

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275

270

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“…In the case of robustness to genetic modifications, some mutants will still have the same phenotype and not be removed by natural selection, so that this type of robustness leads to the accumulation of cryptic variation, i.e., genetic variation without phenotypic variation. Though it does not make any phenotypic difference for the time being, such increased genetic variation sets the stage for rapid future evolution, once the cryptic variation is uncovered by further genetic or environmental changes (Delattre and Félix 2009;Masel and Siegal 2009). Robustness to non-genetic modifications allows organisms to survive in changing environments, and is thus the product of evolution.…”

Section: How Mechanisms Adaptively React To Modification: Robustnessmentioning

confidence: 99%

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

Brigandt

2015

History, Philosophy and Theory of the Life Sciences

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Evolutionary developmental biology (evo-devo) is considered a 'mechanistic science,' in that it causally explains morphological evolution in terms of changes in developmental mechanisms. Evo-devo is also an interdisciplinary and integrative approach, as its explanations use contributions from many fields and pertain to different levels of organismal organization. Philosophical accounts of mechanistic explanation are currently highly prominent, and have been particularly able to capture the integrative nature of multifield and multilevel explanations. However, I argue that evo-devo demonstrates the need for a broadened philosophical conception of mechanisms and mechanistic explanation.Mechanistic explanation (in terms of the qualitative interactions of the structural parts of a whole) has been developed as an alternative to the traditional idea of explanation as derivation from laws or quantitative principles. Against the picture promoted by Carl Craver, that mathematical models describe but usually do not explain, my discussion of cases from the strand of evo-devo which is concerned with developmental processes points to qualitative phenomena where quantitative mathematical models are an indispensable part of the explanation. While philosophical accounts have focused on the actual organization and operation of mechanisms, properties of developmental mechanisms that are about how a mechanism reacts to modifications are of major evolutionary significance, including robustness, phenotypic plasticity, and modularity. A philosophical conception of mechanisms is needed that takes into account quantitative changes, transient entities and the generation of novel types of entities, feedback loops and complex interaction networks, emergent properties, and, in particular, functional-dynamical aspects of mechanisms, including functional (as opposed to structural) organization and distributed, system-wide phenomena. I conclude with general remarks on philosophical accounts of explanation.

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“…These are either buffering through alternative pathways or (partial) redundancy originating from gene duplication and coexpression of homologous genes (Hetherington, 2001;Leonhardt et al, 2004;Briggs et al, 2006;Delattre and Félix, 2009). The latter is relevant for our chosen amiRNA-based approach.…”

Section: Analysis Of Genome-wide Protein Familiesmentioning

confidence: 99%

A Genomic-Scale Artificial MicroRNA Library as a Tool to Investigate the Functionally Redundant Gene Space inArabidopsis

et al. 2013

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Traditional forward genetic screens are limited in the identification of homologous genes with overlapping functions. Here, we report the analyses and assembly of genome-wide protein family definitions that comprise the largest estimate for the potentially redundant gene space in Arabidopsis thaliana. On this basis, a computational design of genome-wide family-specific artificial microRNAs (amiRNAs) was performed using high-performance computing resources. The amiRNA designs are searchable online (http://phantomdb.ucsd.edu). A computationally derived library of 22,000 amiRNAs was synthesized in 10 sublibraries of 1505 to 4082 amiRNAs, each targeting defined functional protein classes. For example, 2964 amiRNAs target annotated DNA and RNA binding protein families and 1777 target transporter proteins, and another sublibrary targets proteins of unknown function. To evaluate the potential of an amiRNA-based screen, we tested 122 amiRNAs targeting transcription factor, protein kinase, and protein phosphatase families. Several amiRNA lines showed morphological phenotypes, either comparable to known phenotypes of single and double/triple mutants or caused by overexpression of microRNAs. Moreover, novel morphological and abscisic acid-insensitive seed germination mutants were identified for amiRNAs targeting zinc finger homeodomain transcription factors and mitogen-activated protein kinase kinase kinases, respectively. These resources provide an approach for genome-wide genetic screens of the functionally redundant gene space in Arabidopsis.

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The evolutionary context of robust and redundant cell biological mechanisms

Cited by 15 publications

References 64 publications

Pervasive robustness in biological systems

Pervasive robustness in biological systems

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

A Genomic-Scale Artificial MicroRNA Library as a Tool to Investigate the Functionally Redundant Gene Space inArabidopsis

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