Hi,
I am forwarding a slightly modified version of my previous post with the same title which was rejected by the FIS list due to the heavy attachments. The most significant addition is written in green. The removed attachments are now replaced by their web addresses from which they can be downloaded free of charge. Best. Sung ________________________________ From: Sungchul Ji Sent: Thursday, April 19, 2018 11:02 AM To: FIS FIS Cc: Sergey Petoukhov; dani...@shirasawa-acl.net; John Stuart Reid; sayer ji; sji.confor...@gmail.com; x...@chemistry.harvard.edu; sbur...@proteomics.rutgers.edu; n...@princeton.edu Subject: The 'Shirasawa phenomenon' or the 'Shirasawa effect" Hi FISers, In 2003, Takuji Shirasawa and his coworkers [1] found that mutating certain amino acids in the hemoglobin molecule (Hb) in mice produced the following effects: (1) increase O_2 consumption and CO_2 production, (2) the conversion of the muscle histology from a fast glycolytic to a fast oxidative type, (3) a mild anemia, and (4) faster running speed. In other words, Shirasawa et al provided a concrete example of molecular changes (e.g., amino acid mutations in Hb) leading to (or associated with) macroscopic physiological changes in whole animals (e.g., anemia, running behavior, etc.). For the convenience of discussions, I am taking the liberty of referring to this finding as the "Shirasawa et al. phenomenon/effect" or, more briefly, the "Shirasawa phenomenon/effect" which may be viewed as the macroscopic version of the Bohr effect [2]. The 'Shirasawa phenomenon/effect' is not limited to hemoglobin. There are now many similar phenomena found in the fields of voltage-gated ion channels, i.e., molecular changes in the amino acid sequences of ion channel proteins leading to (or associated with) macroscopic effects on the human body called diseases [3]. Although the current tendency among practicing molecular biologists and biophysicists would be to explain away what is here called the Shirasawa phenomenon in terms of the microscopic changes "causing" the macroscopic phenomenon in a 1:1 basis, another possibility is that the microscopic changes "cause" a set of other microscopic changes at the DNA molecular level which in turn cause a set of macroscopic changes", in a many-to-many fashion. Current trend: Microscopic change (Hb mutation) ---------> Macroscopic change 1 (Oxygen affinity change of blood) ---------> Macroscopic change 2 (O_2 metabolism<http://7769domain.com/Ad/GoIEx2/?token=RURoMlVLRFhYRytKQUovU21uTjVyMlExUVA0eEoyK29icGtYMENQa1BIbnBDQlpxMlR1Slk5Nk5mUTQweVdFRXl3VmtBMTZKZGtGL1lLcmowWWpLYXp2dkdiYkxLR1k3UEE3OGQwWXRpbGxObkdOOXB1a0RxQjZCZkJ2OFFQTjJHMk85T0VrSEV0YTlHM3VVOS9HbGVFeWJ3ME0rc01VcXZZekpiQmZ2YjRFN040bjRiWkFRbmtBQUhvWWtYS1F60>, anemia, running behavior) Althernative mechanism: Microscopic change 1 (Hb mutation) -------> Microscopic change 2 (Changes in the standing waves in DNA) -------> Multiple macroscopic changes (O_2 metabolism, anemia, muscle cell histological changes). The alternative mechanism proposed here seems to me to be more consistent with the newly emerging models of molecular genetics [4] and single-molecule enzymology [5, 6]. Since the 'Shirasawa phenomenon/effect' evidently implicates information transfer from the microscale to the macroscale, it may be of interest to many information theoreticians in this group. If you have any questions, comments, or suggestions, please let me know. All the best. Sung References: [1] Shirasawa, T., et al. (2003). Oxygen Affinity of Hemoglboin Regulaters O_2 Comsumtion, Metabolism, and Physical Activity. J. Biol. Chem. 278(7): 5035-5043. PDF at http://www.jbc.org/content/278/7/5035.full.pdf [2] The Bohr effect. https://en.wikipedia.org/wiki/Bohr_effect [3] Huang W, Liu M, S Yan F, Yan N. (2017). Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.<https://molbio.princeton.edu/publications/structure-based-assessment-disease-related-mutations-human-voltage-gated-sodium> Protein Cell. 8(6):401-438. PDF at https://www.ncbi.nlm.nih.gov/pubmed/28150151 [4] Petoukhov, S. V. (2016). The system-resonance approach in modeling genetic structures. BioSystems 139: 1–11. PDF at https://www.sciencedirect.com/science/article/pii/S0303264715001732 [5] Lu, H. P., Xun, L. and Xie, X. S. (1998) Single-Molecule Enzymatic Dynamics. Science 282:1877-1882. PDF at http://www.jbc.org/content/274/23/15967.short [6] Ji, S. (2017). RASER Model of Single-Molecule Enzyme Catalysis and Its Application to the Ribosome Structure and Function. Arch Mol. Med & Gen 1:104. PDF at http://hendun.org/journals/AMMG/PDF/AMMG-18-1-104.pdf
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