PNAS 99(16): 10528–10532 (August 6, 2002)
Waddington’s canalization revisited: Developmental stability and evolution
Mark L. Siegal and Aviv Bergman

Most species maintain abundant genetic variation and experience a range of environmental conditions, yet phenotypic variation is low. That is, development is robust to changes in genotype and environment. It has been claimed that this robustness, termed canalization, evolves because of long-term natural selection for optimal phenotypes. We show that the developmental process, here modeled as a network of interacting transcriptional regulators, constrains the genetic system to produce canalization, even without selection toward an optimum. The extent of canalization, measured as the insensitivity to mutation of a network’s equilibrium state, depends on the complexity of the network, such that more highly connected networks evolve to be more canalized. We argue that canalization may be an inevitable consequence of complex developmental–genetic processes and thus requires no explanation in terms of evolution to suppress phenotypic variation.

Waddington developed the concept of canalization to explain the “very general observation… that the wild type of an organism, that is to say, the form which occurs in Nature under the influence of natural selection, is much less variable in appearance than the majority of the mutant races” (1). Corroborating Waddington's observation are a number of experiments demonstrating increased phenotypic variance under extreme genetic or environmental perturbation (2–6). A key insight of Waddington was that the constancy of wild-type phenotypes in the face of genetic and environmental perturbations is best viewed as a buffering of the developmental process. That is, Waddington argued that the evolutionist's traditional focus on the genetic (i.e., hereditary) system must be supplemented by a focus on the epigenetic (i.e., developmental) system (7, 8). Waddington's favored view, evident in the above quotation, is that buffering of the epigenetic system evolves as a result of natural selection, in particular selection toward an intermediate optimum, i.e., stabilizing selection. Naively stated, this conclusion appears self-evident: as long as genetic variation exists, any mechanism that dampens the effects of that variation on the phenotype is expected to be favored by stabilizing selection. It is not surprising, therefore, that most attempts to model mathematically the evolution of canalization begin with Waddington's assumption of stabilizing selection (9–15). As we will see below, the implementation of this assumption can confound the action of natural selection with the process of development, thereby obscuring the role other forces may play in producing a canalized genetic system.

Despite the experimental and theoretical groundwork laid by Waddington, the mechanisms and evolutionary causes and effects of canalization remain elusive. However, in the current era of sophisticated developmental genetics and genome-scale functional analysis, canalization has begun to receive increased attention, both as a potentially solvable puzzle and as a framework for understanding the evolution of complex genomes. For example, Rutherford and Lindquist (6) recently uncovered vast genetic variation by compromising the function of Drosophila Hsp90, a stress-induced chaperone protein that confers stability on a variety of signal-transduction proteins. They conclude that Hsp90 serves as an evolutionary “capacitor,” buffering genetic and environmental variation except under extreme conditions, at which point the expressed variation becomes available for natural selection. This interpretation parallels the link drawn by Waddington between canalization and the inheritance of environment-induced phenotypic variation, or “genetic assimilation” (16), and provides a developmental–genetic mechanism for the breakdown of epigenetic buffering under extreme perturbation. Another perspective on canalization is now offered by the outpouring of genomic sequence and expression data in model organisms. For example, A. Wagner (17) analyzed jointly gene-sequence and gene-expression data on a genome-wide scale in yeast and concluded that robustness of the wild type to mutations is due not to genetic redundancy but to epistatic interactions between unrelated genes. Relying on previous theoretical results, he concluded that this robustness evolved as a response to stabilizing selection.

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Baldwin Effect / Canalization / Genotype-Phenotype Map