Evolution Shapes the Gene Expression Response to Oxidative Stress

Abstract

Reactive oxygen species (ROS) play a key role in cell physiology and function. ROS represents a potential source of damage for many macromolecules including DNA. It is thought that daily changes in oxidative stress levels were an important early factor driving evolution of the circadian clock which enables organisms to predict changes in ROS levels before they actually occur and thereby optimally coordinate survival strategies. It is clear that ROS, at relatively low levels, can serve as an important signaling molecule and also serves as a key regulator of gene expression. Therefore, the mechanisms that have evolved to survive or harness these effects of ROS are ancient evolutionary adaptations that are tightly interconnected with most aspects of cellular physiology. Our understanding of these mechanisms has been mainly based on studies using a relatively small group of genetic models. However, we know comparatively little about how these mechanisms are conserved or have adapted during evolution under different environmental conditions. In this review, we describe recent work that has revealed significant species-specific differences in the gene expression response to ROS by exploring diverse organisms. This evidence supports the notion that during evolution, rather than being highly conserved, there is inherent plasticity in the molecular mechanisms responding to oxidative stress.

Keywords: D-box; DNA damage; ROS; Spalax; cavefish; evolution; light.

Figure 1

Light, reactive oxygen species (ROS) and the D-box enhancer. Schematic representation of how D-box enhancer-driven gene expression is differentially influenced by blue light exposure in mammalian, zebrafish and cavefish cells. In all three cell types light triggers an increase in intracellular ROS levels that in turn activates the p-38 mitogen-activated protein kinase (MAPK) and c-Jun NH₂ terminal kinase (JNK) stress pathways. In zebrafish cells (central panel), this signaling results in the activation of D-box-driven gene expression, ultimately leading to circadian clock entrainment (indicated by the green arrow). In mammalian cells (left panel) and in cavefish cells (right panel) this signaling fails to activate gene expression via the D-box enhancer element and does not entrain the circadian clock. The white arrow starting from the clock and pointing on the D-box element indicates the circadian clock regulation of this enhancer in mammals [132]. The red cross over the clock in the cavefish cells indicates the blind circadian clock observed in these cells [141].

Figure 2

Loss of D-box function in cavefish. Representative in vivo bioluminescence assays performed in zebrafish (blue traces) and cavefish (orange traces) of cells transfected with the D-box enhancer luciferase reporter derived from the zebrafish 6-4 phr promoter [122] (upper part of the figure). Cells were exposed to three different stressors: light-dark cycles (left panel), a UVC pulse (central panel) or 300 μM H₂O₂ (right panel). The grey (right panel) trace indicates luciferase expression of cavefish cells not exposed to H₂O₂ (negative controls). Black and white bars below each panel indicate the lighting conditions.