Biophysical constraints on randomly expressed genes

Vol. 342 no. 6163 pp. 1188-1193
DOI: 10.1126/science.1242975


Genetic Determinants and Cellular Constraints in Noisy Gene Expression

Abstract excerpt (subscription required to read the article): “In individual cells, transcription is a random process obeying single-molecule kinetics. Often, it occurs in a bursty, intermittent manner. The frequency and size of these bursts affect the magnitude of temporal fluctuations in messenger RNA and protein content within a cell, creating variation or “noise” in gene expression.”

My comment to Science Magazine: “The mechanism by which one signaling pathway regulates a second provides insight into how cells integrate multiple stimuli to produce a coordinated response.” — See: Signaling Crosstalk: Integrating Nutrient Availability and Sex (2013). That mechanism is detailed in the context of thermodynamically-controlled nutrient-dependent seemingly futile cycles of protein biosynthesis/degradation and stochastic non-random gene expression, which enables organism-level thermoregulation.

I have found no reason to believe that this integration of thermodynamically controlled organism-level thermoregulation is not also required in E. coli. There is also experimental evidence of it in mammals. See: Feedback loops link odor and pheromone signaling with reproduction (2005).

Across-species evidence of cause and effect is found in experiments that show the molecular mechanisms of nutrient-dependent pheromone-controlled amino acid substitutions are conserved. This brings up the following question.

Should the biophysical constraints of nutrient-dependent pheromone-controlled thermodynamics and organism-level thermoregulation be given primary consideration in attempts to determine whether experimental evidence supports noisy gene expression?

Given experimental evidence of these biophysical constraints, is there any additional experimental evidence that suggests some remaining noise associated with single-molecule kinetics enables de novo creation of receptors that allow nutrients to enter cells where they can be metabolized and become novel blends of species-specific pheromones that control the physiology of reproduction?

I suspect there may be more evidence from physics that includes the role of single-molecule kinetics that should be included. Is that evidence perhaps buried in the laws of physics that attest to entropy? If so, is that evidence confounded by experimental evidence of biophysical constraints on controlled adaptations, which appear to lead to increased organismal complexity?

Author: James Kohl

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