Beyond networks: mechanism and process in evo-devo

Abstract

Explanation in terms of gene regulatory networks (GRNs) has become standard practice in evolutionary developmental biology (evo-devo). In this paper, we argue that GRNs fail to provide a robust, mechanistic, and dynamic understanding of the developmental processes underlying the genotype-phenotype map. Explanations based on GRNs are limited by three main problems: (1) the problem of genetic determinism, (2) the problem of correspondence between network structure and function, and (3) the problem of diachronicity, as in the unfolding of causal interactions over time. Overcoming these problems requires dynamic mechanistic explanations, which rely not only on mechanistic decomposition, but also on dynamic modeling to reconstitute the causal chain of events underlying the process of development. We illustrate the power and potential of this type of explanation with a number of biological case studies that integrate empirical investigations with mathematical modeling and analysis. We conclude with general considerations on the relation between mechanism and process in evo-devo.

Evolvability and robustness: A paradox restored

“…Evolutionary biologists tend to assume that development does not play a major role (Laland et al, 2014;Mayr, 1961;Pigliucci and Müller, 2010;Wallace, 1986) for evolution and can be easily neglected. They assume that the genotypephenotype map can best be approximated through a linear relationship (DiFrisco and Jaeger, 2019;Fisher, 1930;Orr, 2000). Hence, phenotypic variation can be expressed as genotypic variation and evolutionary dynamics can be described by the latter one.…”

“…Hence, phenotypic variation can be expressed as genotypic variation and evolutionary dynamics can be described by the latter one. On the contrary, evolutionary developmental biologists argue that the genotype-phenotype map is highly complex and non-linear (Alberch, 1991;DiFrisco and Jaeger, 2019;Gjuvsland, Vik, et al, 2013;Minelli and Fusco, 2012;Newman and Müller, 2000;Rice, 2002Rice, , 2004Riedl, 1978;G. P. Wagner and Zhang, 2011).…”

Genetic Causation in Complex Regulatory Systems: An Integrative Dynamic Perspective

“…[ 40 ] This example illustrates that the structure of a network does not uniquely determine its function. [ 41 ] It also highlights that the same genetic components can mediate completely opposite dynamic behaviors, depending on tissue‐level context.…”

“…[ 37,38 ] This systems‐level approach, combined with evidence from genetic interventions, yields an integrative dynamic explanation of causal flow through the network with all its redundancy and regulatory feedback. [ 41 ]…”

“…Areas of biology such as developmental genetics are dominated by an explanatory mode in which mechanism is identified with gene regulatory networks. [ 41,79 ] While such networks can account for the different transcriptional states that underlie cell fate determination, they do not explain how populations of cells form tissues, change their spatial locations and shapes, articulate into complex morphologies, and shape organismic behaviors. [ 80 ] The multi‐level dynamic framework of causation we have outlined here may provide the beginnings of a powerful conceptual foundation for examining these complex inter‐level influences.…”