Journal Article

Biological robustness

Kitano, Hiroaki

2004

Overview

Key Points Robustness is a ubiquitous feature of biological systems. It ensures that specific functions of the system are maintained despite external and internal perturbations. System control, alternative (or fail-safe) mechanisms, modularity and decoupling are the underlying mechanisms that produce robustness. Robustness facilitates the evolvability of complex dynamic systems. Evolution, given enough time, might select a robust trait that is tolerant against environmental perturbations. This interlinks the properties of robustness and evolvability. Robustness is ubiquitous in biological systems that have evolved. There are specific architectural requirements for robust and evolvable systems — genetic buffering, robust modules and bow-tie architecture. These architectural requirements are the basis for the system's robustness against environmental perturbations, but congruent with genetic perturbations; they facilitate generation of a flexible phenotype. Systems that are robust involve intrinsic trade-offs. Enhanced robustness against certain perturbations has to be balanced by extreme fragility elsewhere. This robust yet fragile nature, predicted by the highly optimized tolerance (HOT) theory, is a fundamental property of the system that has been optimally designed or has evolved to cope with perturbations. There are also other trade-offs in the system's performance and resource demands. Diseases can be thought of in terms of the exposed fragility of robust yet fragile systems. The design of effective countermeasures requires proper understanding of a system's behavioural and failure patterns. Diabetes mellitus , cancer and HIV infection represent the typical failure of such a system that requires systematic countermeasures to control robustness of an epidemic state. Countermeasures include systematic intervention to control a system's dynamics, attack fragility or introduce decoys to re-establish control. Developing a theory of biological robustness with a solid mathematical foundation that can realistically represent biological systems is a difficult challenge. Research into non-linear dynamics, control theory and non-equilibrium theory is urgently required, but it has to be careful to capture the essential structural complexity and heterogeneity of biological systems. Robustness is a ubiquitously observed property of biological systems. It is considered to be a fundamental feature of complex evolvable systems. It is attained by several underlying principles that are universal to both biological organisms and sophisticated engineering systems. Robustness facilitates evolvability and robust traits are often selected by evolution. Such a mutually beneficial process is made possible by specific architectural features observed in robust systems. But there are trade-offs between robustness, fragility, performance and resource demands, which explain system behaviour, including the patterns of failure. Insights into inherent properties of robust systems will provide us with a better understanding of complex diseases and a guiding principle for therapy design.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Adaptation / Adaptation, Biological / Agriculture / Animal Genetics and Genomics / Animals / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cell cycle / Disease / Feedback / Fundamental and applied biological sciences. Psychology / Gene Function / Genetics of eukaryotes. Biological and molecular evolution / Genomes / Human Genetics / Human immunodeficiency virus / Humans / Mutation / Network topologies / Principles / review-article