Stress, genomic adaptation, and the evolutionary trade-off

Abstract

Cells are constantly exposed to various internal and external stresses. The importance of cellular stress and its implication to disease conditions have become popular research topics. Many ongoing investigations focus on the sources of stress, their specific molecular mechanisms and interactions, especially regarding their contributions to many common and complex diseases through defined molecular pathways. Numerous molecular mechanisms have been linked to endoplasmic reticulum stress along with many unexpected findings, drastically increasing the complexity of our molecular understanding and challenging how to apply individual mechanism-based knowledge in the clinic. A newly emergent genome theory searches for the synthesis of a general evolutionary mechanism that unifies different types of stress and functional relationships from a genome-defined system point of view. Herein, we discuss the evolutionary relationship between stress and somatic cell adaptation under physiological, pathological, and somatic cell survival conditions, the multiple meanings to achieve adaptation and its potential trade-off. In particular, we purposely defocus from specific stresses and mechanisms by redirecting attention toward studying underlying general mechanisms.

Keywords: chromosomal instability; genome instability; genome theory; somatic evolution; stress response.

FIGURE 1

Diagram illustrating the relationship between stress, genome topology alteration, resulting genetic network reorganization, and successful evolutionary selection. Different chromosomes are designated by color (red, yellow, blue) and drawn within the nucleus, representing the genome, and genes are designated A, B, C, D, E, F within the chromosomes. Corresponding protein networks are illustrated by the relationships between proteins A, B, C, D, E, F. A cell is exposed to a moderate level of stress (A), resulting in genetic and/or epigenetic alteration as indicated by asterisks (*) next to impacted proteins. The cell survives the stress event without genome-level alteration. When a cell is exposed to a high-level of stress (B), this results in genome topology alteration represented by numerical aberrations (e.g., aneuploidy) and/or structural aberrations (e.g., translocations). This directly affects the physical three-dimensional relationship between genes and changes the overall genetic network structure, resulting in drastic systemic changes beyond the influence of genetic and/or epigenetic alterations that may concurrently occur. As a consequence, the corresponding protein network changes are shown by altered relationships between proteins. These new genomic systems then undergo evolutionary selection, and those that are stochastically selected upon may clonally expand and dominate the cell population.