Organisms often show robustness to genetic or environmental perturbations. Whether these two components of robustness can evolve separately is the focus of the paper by Le Rouzic [1]. Using theoretical analysis and individual-based computer simulations of a gene regulatory network model, he shows that multiple aspects of robustness can be investigated as a set of pleiotropically linked quantitative traits. While genetically correlated, various robustness components (e.g., mutational, developmental, homeostasis) of gene expression in the regulatory network evolved more or less independently from each other under directional selection. The quantitative approach of Le Rouzic could explain both how unselected robustness components can respond to selection on other components and why various robustness-related features seem to have their own evolutionary history. Moreover, he shows that all components were evolvable, but not all to the same extent. Robustness to environmental disturbances and gene expression stability showed the largest responses while increased robustness to genetic disturbances was slower. Interestingly, all components were positively correlated and remained so after selection for increased or decreased robustness.

This study is an important contribution to the discussion of the evolution of robustness in biological systems. While it has long been recognized that organisms possess the ability to buffer genetic and environmental perturbations to maintain homeostasis (e.g., canalization [2]), the genetic basis and evolutionary routes to robustness and canalization are still not well understood. Models of regulatory gene networks have often been used to address aspects of robustness evolution (e.g., [3]). Le Rouzic [1] used a gene regulatory network model derived from Wagner’s model [4]. The model has as end product the expression level of a set of genes influenced by a set of regulatory elements (e.g., transcription factors). The level and stability of expression are a property of the regulatory interactions in the network.

Le Rouzic made an important contribution to the study of such gene regulation models by using a quantitative genetics approach to the evolution of robustness. He crafted a way to assess the mutational variability and selection response of the components of robustness he was interested in. Le Rouzic’s approach opens avenues to investigate further aspects of gene network evolutionary properties, for instance to understand the evolution of phenotypic plasticity.

Le Rouzic also discusses ways to measure his different robustness components in empirical studies. As the model is about gene expression levels at a set of protein-coding genes influenced by a set of regulatory elements, it naturally points to the possibility of using RNA sequencing to measure the variation of gene expression in know gene networks and assess their robustness. Robustness could then be studied as a multidimensional quantitative trait in an experimental setting.

References

[1] Le Rouzic, A (2022) Gene network robustness as a multivariate character. arXiv: 2101.01564, ver. 5 peer-reviewed and recommended by Peer Community in Evolutionary Biology. https://arxiv.org/abs/2101.01564

[2] Waddington CH (1942) Canalization of Development and the Inheritance of Acquired Characters. Nature, 150, 563–565. https://doi.org/10.1038/150563a0

[3] Draghi J, Whitlock M (2015) Robustness to noise in gene expression evolves despite epistatic constraints in a model of gene networks. Evolution, 69, 2345–2358. https://doi.org/10.1111/evo.12732

[4] Wagner A (1994) Evolution of gene networks by gene duplications: a mathematical model and its implications on genome organization. Proceedings of the National Academy of Sciences, 91, 4387–4391. https://doi.org/10.1073/pnas.91.10.4387