Genetic causation in complex regulatory systems: An integrative dynamic perspective
Abstract
The logic of genetic discovery has changed little over time, but the focus of biology is shifting from simple genotype-phenotype relationships to complex metabolic, physiological, developmental, and behavioral traits. In light of this, the traditional reductionist view of individual genes as privileged difference-making causes of phenotypes is re-examined. The scope and nature of genetic effects in complex regulatory systems, in which dynamics are driven by regulatory feedback and hierarchical interactions across levels of organization are considered. This review argues that it is appropriate to treat genes as specific actual difference-makers for the molecular regulation of gene expression. However, they are often neither stable, proportional, nor specific as causes of the overall dynamic behavior of regulatory networks. Dynamical models, properly formulated and validated, provide the tools to probe cause-and-effect relationships in complex biological systems, allowing to go beyond the limitations of genetic reductionism to gain an integrative understanding of the causal processes underlying complex phenotypes.
Journal details
Journal BioEssays
Volume 42
Issue number 6
Pages e1900226
Available online
Publication date
Full text links
Publisher website (DOI) 10.1002/bies.201900226
Europe PubMed Central 32449193
Pubmed 32449193
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