The plasticity of the genetic material: concepts and applications Carlos Bloch Jr. Mass Spectrometry Laboratory EMBRAPA Genetic Resources and Biotechnology – Brazilian Agriculture Research Corporation. Brasília-DF, Brazil. DNA, RNA, and proteins are the informational molecules of life. All living cells are made by numerous “molecular words” (building blocks) encoded as constitutive parts of the structures of these rather long molecules, which have been under increasing investigation by several genome and proteome project world-wide 1,2 for quite some time. The ever-growing knowledge emerging from the Molecular Biology and the Biochemistry fields shows that these “words” which in the past were thought to embody a fixed command or biological function inside the cell machinery - may also comprise other meanings in the living metabolism and in the cell physiology with substantial implication on the health and for the surviving fitness of many species that were not perceived as such by the researchers until lately. For more than two decades, taking advantage of the massive amount of data produced by all publicly available genome and proteome sequencing initiatives, our research group collected empirical evidence and developed experimental methodologies to demonstrate that proteins (or parts of them) - encoded by certain specie’s genome - exhibit other biological roles very different from those previously identified and therefore recognized by the scientific community. In short, there are many reports 3,4 from various research groups showing that proteins canonically described based on their leading biological functions, such as the blood hemoglobin (carrier of O2 and CO2 during the breathing process in animals) and casein (from milk), also contain internal fragments - smaller parts of the complete molecule - that present one or more biological activities previously unimagined and unrelated to their main ones. Our research5,6,7 have been confirming that those early third part findings were not an exception to rule, restricted to just few examples, or simply fortuitous novelties. Indeed, many other proteins were also found to have encrypted biological functions hidden inside shorter segments of their whole primary structures and, by analogy, poorly comparable to the Russian matryoshka dolls, where each sequential smaller doll would have different biological function when compared to the preceding one. So far, the most recent results 7,8 on this subject obtained by our group and others indicate that the genetic material of living cells may contain potentialities and molecular plasticity to favor life on Earth under the most distinct range of adaptive conditions yet to be revealed and comprehended. It is common knowledge that the whole molecular information present in the genomes of all living cells is stored in modules, called genes. However, all facts and reasoning discussed above imply that these modules, apparently contain sub-modules that can only become functional after the complete physiological maturation of the first one, i.e., at a subsequent metabolic level of the major gene expression event. This hierarchical double-stage potentialities actualization of the bulk genetic material, to my best understanding, suggests the existence of an ordered and refined process that occurs after the latest event of the embodiment of the prime matter of life, yet to be better described and understood biologically. Furthermore, it also points out to a kind of resourceful intelligence behind its origin that, in turn, could be emulated to produce useful methodologies to tackle real problems of human health, animal welfare and agriculture, as our research group has already demonstrated5,6,7,9,10. Finally, after decades of exposure to the facts and thoughts briefly announced here, we ask both from a scientific and philosophical perspective, what is the unifying nature of the relationships that holds the hierarchical structure together and if this unity is best explained through a “top-down” or a “bottom-up” methodology (or both)? References: 1. H. A. Lewin et al. (2018); Earth BioGenome Project: Sequencing life for the future of life. PNAS 115 (17):4325-4333. 1 2. 3. 4. 5. 6. 7. 8. 9. 10. G. S. Omenn. (2021); Reflections on the HUPO Human Proteome Project, the Flagship Project of the Human Proteome Organization, at 10 Years. Molecular Cell Proteomics 20:100062. V.

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