Searching for Non-random Genome Editing Mechanisms

Dear Colleagues,

There is a body of evidence regarding eukaryotic species that suggests the existence of some “smart” non-random genome editing mechanisms capable of “accelerating” organism adaptation to environmental changes. Searching for non-random genome editing mechanisms, there is one fascinating example in the immune system called somatic hypermutation (SHM) of immunoglobulins. This is a mechanism that, starting from the genome of a single B cell, is able to induce random mutations exclusively in the immunoglobulin gene, “non-randomly” leaving the rest of the genome intact. When immune recognition of pathogens is at low affinity, pathogens are not eliminated; therefore, low affinity immunoglobulin gene is continuously transcribed (“hyper-transcribed”). In this case, hyper-transcribed intronic retrotransposons of the immunoglobulin gene produced in response to chronic pathogen/environmental stress conditions can guide AID mutagenic enzyme to opened chromatin regions of the same “hyper-transcribed” immunoglobulin gene, surgically inducing its mutation. This mechanism is able to generate different immunoglobulin phenotypes, finally providing the raw material for selection of the most environmentally effective immunoglobulin/phenotype. Moreover, during host–pathogen conflicts, there are some special adaptations that lead not only to organism but also to pathogen survival inside the organism; a sort of agreement in which they potentiate each other to promote a synergistic survival effect also called symbiosis. These are the most stable biological solutions that are repetitively selected along the struggle for survival, finally generating “holobiontic” organisms. During iterative attempts of genome editing, new (immunoglobulin) genes, but also new (immune) mechanisms (e.g., SHM), can be generated, selected, and inherited, when they provide survival advantage. In this view, the immune system can be considered a “military” biotechnological laboratory that, “trained” by pathogens, develops “smart” bio-molecular technologies which are ultimately exapted for “civil” purposes, i.e., adaptation of organisms as whole. However, to vertically transmit them to progeny for species adaptation, novel somatic biotechnological tools built up by immune system have to be subsequently shared with other organs, including germline cells possibly through horizontal genomic transfer.

I have recently described how cellular proteins in an organism can be modified similarly to immunoglobulins, plastically adapting them to new “pollutants” interfering with their functions. In order to compensate the reduced protein function due to pollutant interference, cells increase protein transcription (and amount), leading to its specific gene hyper-transcription. However, genes that are transcribed at their maximum rate (hyper-transcribed) yet are still unable to meet new chronic environmental demands, are inadequate and generate more and more intronic retrotransposons. Finally, retrotransposon-guided mutagenic enzymes would be able to edit hyper-functional 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. However, non-random genome editing mechanisms, depending on the individual genomic background and environmental changes, can lead to outcomes ranging from organismal adaptation and survival to chronic diseases and death of environmentally inadequate genomes. For example, the induction of random and iterative genetic attempts could generate new (self) proteins that could be recognised as extraneous (non-self) by the immune system, leading to autoimmune responses.

In the present Special Issue of Cells, experts in the field will describe the state-of-the-art of non-random genome editing mechanisms and their involvement both in the evolutionary processes of adaptation and in the underlying causes of diseases.

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

Dr. Loris Zamai
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Dr. Loris Zamai
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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