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  • Review Article
  • Published:

Pervasive robustness in biological systems

Nature Reviews Genetics volume 16, pages 483–496 (2015)Cite this article

Subjects

Key Points

  • The 'robustness' of a phenotypic trait is the absence or low level of variation when faced with a given incoming variation.

  • Analysis of the propagation of variation in a biological system has been approached differently in evolutionary quantitative genetics and in systems biology studies, but a new unifying approach is now possible.

  • The robustness of a downstream phenotype to a range of variation in an upstream component may be explained by pervasive nonlinearities and plateaus in quantitative relationships between system components.

  • Many recent reports of robustness-conferring genes do not distinguish between effects on phenotypic mean and variance, and therefore are just another way to refer to the low penetrance and condition-dependence of mutations.

  • A robust feature is not necessarily an evolutionary advantage and may have arisen under neutral evolution or through pleiotropy.

Abstract

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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Figure 1: Robustness of a phenotype to an incoming variation.
Figure 2: Nonlinear relationships between gene activity and phenotype.
Figure 3: Mechanisms of developmental robustness.
Figure 4: Two definitions of robustness-conferring genes, with and without change of the phenotypic mean.

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Acknowledgements

We thank P. Phillips, C. Braendle, V. Orgogozo, V. Debat, E. Andersen, F. Besnard and the reviewers for comments on the manuscript, N. Dostatni and H. Teotonio for discussions, and S. Rifkin for introducing us to Rendel. Work on developmental robustness in the Félix laboratory is funded by the Agence Nationale pour la Recherche (12-BSV2-0004-01) and a Coup d'Elan from the Bettencourt-Schueller Foundation; work in the Barkoulas laboratory is funded by the Biotechnology and Biological Sciences Research Council (BBSRC) in the UK (BB/L021455/1).

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Authors and Affiliations

  1. Institute of Biology of the Ecole Normale Supérieure, CNRS UMR8197, INSERM U124, ENS, 46 rue d'Ulm, Paris, 75005, France

    Marie-Anne Félix

  2. Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, SW7 2AZ, UK

    Michalis Barkoulas

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  1. Marie-Anne Félix
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Correspondence to Marie-Anne Félix.

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PowerPoint slides

Glossary

Robustness

Invariance or low variation of a given phenotype when faced with a given incoming variation. Used synonymously with insensitivity.

Sensitivity

Variation of a given phenotype when faced with a given incoming variation.

Variance

A measure of variation in a distribution, defined as the sum of squared deviations of individual points to the mean.

Stochastic variance

Variation of the phenotype when faced with uncontrollable noise; also called microenvironmental variance.

Genetic variance

Variation of the phenotype when faced with a given set of genetic variation.

Canalization

A process by which the phenotypic variance of a trait is reduced when faced with a given perturbation.

Variational features

A specific instance of the propagation of variation from an incoming variation to a given phenotype. The incoming variation may be stochastic, environmental or genetic.

Robust features

A particular case of variational feature where the phenotype is robust to the incoming variation.

Plasticity

Variation of a phenotype when faced with a given environmental variation.

Intermediate phenotype

Also known as endophenotype. An intermediate developmental trait in the construction of the phenotype of interest.

Standing genetic variation

Allelic variation that is currently segregating in a given population, in contrast to alleles that arise by new mutation events.

Incoming variation

The perturbation that is considered for a given variational feature.

Cryptic genetic variation

Genetic variation that is silent for the trait of interest but is not silent for some variables in the underlying system.

Fluctuating asymmetry

Measure of variation between the right and left sides of the body, taken as a measure of sensitivity to developmental noise.

Norm of reaction

(Also known as reaction norm). Function or plot linking the phenotype (y-axis) to the environmental variable (x-axis), for a given genotype.

Coefficient of variation

Dimensionless measure of variation in a distribution corresponding to the square root of the variance (standard deviation) over the mean.

Pleiotropy

Alteration of more than one phenotype by the same genetic variant.

Stabilizing selection

Selection that tends to eliminate extreme phenotypic variants. This results in reduced phenotypic variance and robustness of the trait under selection.

Mutational variance

A particular case of genetic variance, where the relevant genetic variation is a random mutation.

Epistasis

Non-additive effect of two genetic variations on the phenotype.

System parameter space

Multidimensional space of quantitative parameters characterizing a system.

Congruence

Similarity between the responses to different sources of variation — for example, environmental and genetic.

Nonlinearity

Relationship between two variables (input and output) that is not proportional.

Coherent feedforward motifs

Networks in which the downstream effects of a gene reinforce each other.

Incoherent feedforward motifs

Networks in which the downstream effects of a gene antagonize each other.

Paradoxical regulation

A two-component network in which the downstream effects of a gene antagonize each other.

Probit

Distance to the mean in standard deviations of a frequency distribution, computed as the inverse of the standard normal cumulative distribution function.

Phenodeviants

Individuals with a phenotype outside a defined normal range within a reference population.

Phenotypic capacitors

Genes that, when mutated or deleted, lead to an increase in phenotypic variance in response to a given perturbation.

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Félix, MA., Barkoulas, M. Pervasive robustness in biological systems. Nat Rev Genet 16, 483–496 (2015). https://doi.org/10.1038/nrg3949

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