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.

Behavior of replication origins in Eukaryota – spatio-temporal dynamics of licensing and firing

“…Alzheimer disease or autism. 19 Such alterations of the genetic material raise the probability of somatic evolution. 20 However, the massive DNA replication missbehavior can lead to genome chaos, genome instability and -in this context -can be perceived as relevant to cancer biology.…”

Replication and re-replication: Different implications of the same mechanism

“…skeletal muscles, liver cells etc. [42]. Such alterations of genetic material raise the probability of somatic evolution [43].…”

“…A low level of stress results in non-genetic response pathways, medium level of stress results in gene and/or epigenetic changes while high level of stress leads to genome-level reorganization. High levels of stress can lead to genome shattering and reorganization which is called genome chaos [39,42]. Chromoplexy e a number of chain-like rearrangements placed in close location was found to be important in the evolution of prostate cancer.…”

Evolutionary mechanism unifies the hallmarks of cancer

“…As a trade-off, they also contribute to the increased potential for cancer in the longterm. 47,48 Second, most individual runs of cancer evolution are not successful within the human body due to the multiple levels of system constraint and the low probability of the "perfect storm" required by cancer to become clinically significant. 1 Breakdown of system constraint (for example through the aging process or prolonged high stress cellular conditions) is the major contributing factor for successful cancer evolution.…”