Fold-change detection in biological systems

Abstract

Many sensory systems in cells and organisms share a recurring property called fold-change detection (FCD). FCD describes a system whose dynamics – including amplitude and response time – are determined only by the relative change in input signal, rather than its absolute change. FCD entails two important features – exact adaptation and the Weber–Fechner law. Systems with FCD include bacterial and eukaryotic chemotaxis, signaling pathways in mammalian cells such as NF-κB, Wnt and Tgf-β, and organismal vision, hearing and olfaction. Here, we review circuits that can provide FCD such as the incoherent type 1 feedforward loop, the non-linear integral feedback loop, and logarithmic sensor. We review experimental ways to test for FCD and differentiate between FCD mechanisms, and highlight theoretical studies that begin to map the space of FCD circuits and the functions they can provide. Finally, we discuss open questions on the structure and function of FCD systems.