Mutation plus mutation: restoration with as yet undetected imbalance

Genetic mutation found to restore translational balance in mice

Excerpt:”…the prime cause of the Fragile X syndrome may be a translational imbalance that results in elevated protein production in the brain. Restoration of this balance may be necessary for normal neurological function.

“Biology works in strange ways,” said Joel Richter, PhD, professor of molecular medicine at UMMS and senior author on the study. “We corrected one genetic mutation with another, which in effect showed that two wrongs make a right. Mutations in each gene result in impaired brain function, but in our studies, we found that mutations in both genes result in normal brain function. This sounds counter-intuitive, but in this case that seems to be what has happened.”

My comment: In my model of adaptive evolution, the nutrient-dependent pheromone-controlled microRNA / messenger RNA (miRNA/mRNA) balance results is protein biosynthesis and degradation in tissues of the brain and body. Mutations perturb the miRNA/mRNA-controlled translational balance. Mutations result in detrimental effects on thermodynamic regulation of intercellular signaling, intramolecular interactions, alternative splicings and stochastic gene expression. This links epigenetic effects of  nutrient stress and social stress to physical diseases and mental disorders via the conserved molecular mechanisms of ecological, social, neurogenic, and socio-cognitive niche construction. Transgenerational epigenetic effects are included.

Two mutations cannot correct disordered brain function.  Similarly, one mutation or two mutations or any number of mutations in any gene of any species cannot lead to adaptive evolution, which is clearly nutrient-dependent and pheromone-controlled in species from microbes to man.

Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology [subscription required]

Abstract excerpt: “…we find that FMRP and CPEB1 balance translation at the level of polypeptide elongation. Our results suggest that disruption of translational homeostasis is causal for FXS and that the maintenance of this homeostasis by FMRP and CPEB1 is necessary for normal neurologic function.”

My comment: Mutations disrupt translational homeostasis by disrupting the miRNA/mRNA balance.  Biology does not work in strange ways. Maintenance of homeostasis by FMRP and CPEB1 is perturbed by the effect of mutations on either FMRP or on CPEB1. Attempts to restore homeostasis that involve pitting one mutation against another may result in what appears to stabilize polypeptide elongation at one level of organization. But the mutations will result in perturbed homeostasis of downstream brain functions that are necessary for normal neurologic function, but not necessarily linked to either FMRP or CPEB1.

As the medical model of diseases continues to include genotoxic drugs with unknown epigenetic effects across networks of interactive genes, it becomes more important to understand the basic principles of biology and levels of biological organization that link cause and effect to typical and atypical development in species from microbes to man. Clearly more than two genes interact. They started with the frog, but probably should have started with yeasts, since it is perfectly clear that even the behavior of brainless microbes is nutrient-dependent and pheromone-controlled and that the number of gene x gene and gene x environment interactions cannot be reduced to the results from a study of two mutations in fragile X pathophysiology.


About James V. Kohl 1308 Articles
James Vaughn Kohl was the first to accurately conceptualize human pheromones, and began presenting his findings to the scientific community in 1992. He continues to present to, and publish for, diverse scientific and lay audiences, while constantly monitoring the scientific presses for new information that is relevant to the development of his initial and ongoing conceptualization of human pheromones. Recently, Kohl integrated scientific evidence that pinpoints the evolved neurophysiological mechanism that links olfactory/pheromonal input to genes in hormone-secreting cells of tissue in a specific area of the brain that is primarily involved in the sensory integration of olfactory and visual input, and in the development of human sexual preferences. His award-winning 2007 article/book chapter on multisensory integration: The Mind’s Eyes: Human pheromones, neuroscience, and male sexual preferences followed an award winning 2001 publication: Human pheromones: integrating neuroendocrinology and ethology, which was coauthored by disinguished researchers from Vienna. Rarely do researchers win awards in multiple disciplines, but Kohl’s 2001 award was for neuroscience, and his 2007 “Reiss Theory” award was for social science. Kohl has worked as a medical laboratory scientist since 1974, and he has devoted more than twenty-five years to researching the relationship between the sense of smell and the development of human sexual preferences. Unlike many researchers who work with non-human subjects, medical laboratory scientists use the latest technology from many scientific disciplines to perform a variety of specialized diagnostic medical testing on people. James V. Kohl is certified with: * American Society for Clinical Pathology * American Medical Technologists James V. Kohl is a member of: * Society for Neuroscience * Society for Behavioral Neuroendocrinology * Association for Chemoreception Sciences * Society for the Scientific Study of Sexuality * International Society for Human Ethology * American Society for Clinical Laboratory Science * Mensa, the international high IQ society