Searching for Non-random Genome Editing Mechanisms: Pathogen-Induced Immune Mechanism Evolution and Immune Mechanism Exaptation for Organism Adaptation and Evolution

Dear Colleagues,

There is a body of unexplainable “weird” evidence regarding eukaryotic species that suggests the existence of some “smart” nonrandom genome editing mechanisms. In this regard, the immune system can be considered a “military” biotechnological laboratory that, “trained” by pathogens, develops "smart" biomolecular technologies which are ultimately exapted for “civil” purposes, i.e., adaptation of organisms as whole. Indeed, being pushed due to survival conflicts with pathogens, the immune system produces random and iterative attempts to counter pathogen threats that are not necessarily aimed at excluding the foreigner but, rather, to select the most virus–host compatible structures. Most notably are some adaptive genetic attempts to generate new (self) proteins that can be recognised as extraneous (non-self) by the immune system, leading to an autoimmune response. On the other hand, some microorganisms in persistent interaction with an organism become an integral part of the organism and are not threatened by the immune system. Therefore, the immune system, rather than discriminating between self and non-self, seems to ultimately work as a scavenger that, by eliminating “inadequate” attempts, finally allows the selection of the most self-compatible and symbiotic structures. Among these iterative attempts, there are some special ones that lead to not only organism but also pathogen survival inside the organism; a sort of agreement in which they potentiate each other to promote a synergistic survival effect also called symbiosis or symbiogenesis. These are the most stable biological solutions that are repetitively selected along the struggle for survival, finally generating holobiontic organisms. These organisms are able to cohabit with microorganisms and to store more and more epigenetic and genetic information in their large eukaryotic genomes. Nevertheless, they still maintain genomic flexibility and adaptability to environmental changes through stress-induced nonrandom genome editing mechanisms. Indeed, during host–pathogen conflicts, genome editing events are randomly generated and those which can produce effective pathways of survival advantage, are selected and memorised, and become novel reproducible “mechanisms”. One example of these mechanisms is the somatic hypermutation (SHM) of immunoglobulins, in which the single-cell genome of a B cell can generate different cell phenotypes as a function of environmental stress conditions. Immunoglobulin gene plasticity induced by random immunoglobulin gene mutation is activated in response to chronic presence of pathogen antigens and provides the raw material for selection of the most environmentally effective phenotype. Notably, within the huge eukaryotic genome, there is a nonrandom and exclusive targeting of the immunoglobulin gene in which random mutations are induced, leaving the rest of the genome intact. Novel somatic biotechnological tools built up by immune system (e.g., SHM) are then shared through horizontal genomic transfer with other organs, including germline cells which ultimately transmit them to progeny for species adaptation. Indeed, I have recently described how the majority of cell proteins in an organism can modify their structures similarly to SHM, plastically adapting them to new “pollutants” interfering with their functions. Interference of a pollutant with a cell protein is able to induce its specific gene hypertranscription. However, genes that are transcribed at their maximum rate (hypertranscribed) yet are still unable to meet new chronic environmental demands, are environmentally inadequate and generate more and more intronic retrotransposons. Finally, retrotransposon-guided mutagenic enzymes would be able to edit hyperfunctional and inadequate genes, generating several cell mutants, and those codifying for the most environmentally adequate proteins would have a survival advantage and, therefore, would be Darwinianly selected. Such mechanisms represent the exaptation of an antiviral mutagenic mechanism (i.e., SHM) into nonrandom genome editing mechanisms directed at “hypertranscribed” endogenous genes of the entire organism. Transposon-guided mutagenic enzymes and horizontal “genomic” transfer are some of the biological technologies developed through pathogen training and pathogen domestication to predispose life to counteract present challenges and to prevent future unpredictable environmental threats and were therefore “naturally” selected. However, nonrandom genome editing mechanisms, depending on the individual genomic background and environmental changes, can lead to outcomes ranging from adaptive survival and evolutionary advantage or, alternatively, to chronic diseases and death of environmentally inadequate genomes. In the present Special Issue of Cells, experts in the field will describe the state-of-the-art of nonrandom genome editing mechanisms and their involvement both in the past steps of the evolutionary processes and in the present as underlying causes of novel adaptations or diseases.

We are looking forward to your contributions to this Special Issue. 

Prof. Loris Zamai
Guest Editor

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• virus
• immune system
• pollution
• environmental stress
• retrotransposons
• mutagenic enzymes
• symbiosis
• horizontal genomic transfer
• transgenerational non-Mendelian gene transmission
• chronic diseases