In This Article Expand or collapse the "in this article" section Systems Biology

  • Introduction
  • Journals
  • Comparative Functional Genomics
  • Epistasis and the Genotype-Phenotype Map
  • Systematic Study of the Genotype-Phenotype Map
  • Robustness
  • Rewiring of Regulatory Systems
  • Modularity and Evolvability
  • Evolutionarily Relevant Variants in Biological Networks
  • Stochasticity and Adaptive Heterogeneity

Evolutionary Biology Systems Biology
Yevgeniy Plavskin, Mark L. Siegal
  • LAST REVIEWED: 13 December 2021
  • LAST MODIFIED: 26 September 2022
  • DOI: 10.1093/obo/9780199941728-0010


The exact meaning of the term systems biology is debated, yet most biologists agree that it refers to the study of organismal properties that cannot be reduced to the functions of single genes or other individual components. That is, systems biology is about the traits—be they physiological, developmental, or behavioral—that arise out of interactions between components. Some systems biologists emphasize not the subject matter of the field, but instead the methodology, which combines experimental perturbations with high-throughput quantitative measurements and mathematical modeling. The goal is to understand how complex biological systems achieve function through iterative cycles of data gathering and model-based prediction. Evolutionary biology intersects with systems biology in two ways. First, evolution provides a means of understanding the current structure and function of biological systems. For example, many studies have found that networks of biological interactions do not have topologies consistent with random connections between pairs of components. The departures from random expectation must have evolutionary explanations, and both adaptive and nonadaptive explanations have been proposed and debated. Second, systems biology holds the promise of replacing unrealistically simple representations of the mapping between genotype and phenotype —a key element of all evolutionary models—with more meaningful ones. Thus, systems biology can expand and enrich our understanding of complex-trait evolution. This article aims to provide entry points into the literature of evolutionary systems biology from its historical roots to its current incarnations. Particular attention is paid to the organizational features and functional properties of complex biological systems. System organization is typically investigated in terms of networks of interacting components, such as genes or proteins. Organizational features of interest range from the global level of overall network topology to the local level of modules and regulatory motifs. Functional properties of interest include modularity, evolvability, and robustness to perturbations, such as environmental fluctuations and mutations. The field of evolutionary systems biology spans a range of organisms and analytical approaches, addresses a range of questions, and, indeed, has several alternative definitions. The works compiled here were chosen to reflect this diversity, to highlight major developments and insights, and to enable more extensive forays into the literature.

General Overviews

Although the field of systems biology has roots going back decades (see Forerunners of Modern Systems Biology), most scientists would place the start of its modern form around the late 1990s or early 2000s. The first review articles heralding the new field appeared in the early 2000s, whereas the first textbooks appeared a few years later (see Systems Biology). Although the foundational works of evolutionary systems biology emerged at about the same time as those of modern systems biology (see Historical Background), the field was not called evolutionary systems biology until around 2004 (see O’Malley 2012, cited under Alternative Definitions). Reviews and edited volumes on evolutionary systems biology followed soon after that (see Evolutionary Systems Biology).

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