Synthetische Genomik: von der DNA‐Synthese zu Designer‐Genomen

Abstract

Rasante technische Fortschritte, die die Konstruktion von genetischen Netzwerken, Biosynthesepfaden und sogar ganzer Genome ermöglichen, konvertieren derzeit die Genetik und Genomik von rein deskriptiven zu synthetischen Wissenschaften. Anknüpfend an die Synthese kleiner viraler Genome haben Fortschritte bei der Assemblierung und Neusynthese von DNA die hierarchische Synthese bakterieller Genome, z. B. von Mycoplasma genitalium, sowie die Umkodierung des Genoms von Escherichia coli durch Reduzierung der Zahl an Codons von 64 auf 57 ermöglicht. Das Gebiet ist an dem Punkt angekommen, dass wir ein gesamtes eukaryotisches Genom synthetisieren können. Das “Synthetic Yeast Genome Project” (Sc2.0) folgt den Plan, bis 2018 alle 16 Saccharomyces cerevisiae‐Chromosomen neu zu synthetisieren; bisher wurden 6.5 Chromosomen konzipiert und synthetisiert. Bottom‐up‐Assemblierung und die Anwendung genomweiter Modifikationen werden unser Verständnis der Genomstruktur und ‐funktion verbessern. Dieser Ansatz wird nicht nur eine Plattform für die systemische Erforschung eukaryotischer Chromosomen bieten, sondern auch “verschlankte” Stämme hervorbringen, die für medizinische und industrielle Anwendungen potenziell geeignet sind. In diesem Kurzaufsatz fassen wir den aktuellen Stand der Forschung im Bereich synthetischer Genome zusammen und diskutieren mögliche Anwendungen dieser neuen Technologie.

Decoding semiotic minimal genome: a non-genocentric approach

“…Under this perspective, the main challenge lies on identifying essential elements on the complete genome, regardless of their coding or non-coding traditional classification status. This new paradigm allows for both Top-bottom and Bottom-top approximations to a minimum genome (Wang et al, 2018 ; Rees-Garbutt et al, 2020 ) can benefit from a shift in focus on how information flow is perceived. Instead of a gene-to-functional-product perspective, artificial intelligence tools can be implemented using an information-based genomic-element analysis approach to support both types of laboratory procedures.…”

“…As a result, they obtained the minimum number of genes required for cell reproduction, which included known genes and many others whose functions were unknown. The JCVI-syn3.0 model and other efforts performed on natural organisms (Gil and Peret, 2015 ; Baby et al, 2018 ) with only essential functions that confer reproductive capability in highly controlled conditions (Baby et al, 2018 ; Wang et al, 2018 ) are focused only on the genes involved. Given this scenario, differential gene expression tends to be overlooked, and, consequently, expression regulation elements are usually ignored in minimal genome research.…”

“…To adequately categorize genes into such classification, their functionality regarding cellular autonomy should be considered. The analysis of an obligate parasite or a synthetic organism that has specific environmental condition requirements for its autonomy establishes the challenge to determine where to draw the line to consider the organism as autonomous (Wang et al, 2018 ; Breuer et al, 2019 ). This classification should consider its biological state: whether its single-celled or multi-cellular, and what its environmental and habitat conditions are.…”

“…Each of these biological states will present different complexity levels in terms of adaptability, quorum sensing, and specialization, involving not only genetic expression regulation but also complex information management (Bartha et al, 2018 ; Rosconi et al, 2022 ). We consider important to highlight that minimum genome research has been mainly performed on obligate parasites (Gil and Peret, 2015 ; Baby et al, 2018 ) and/or in controlled laboratory conditions (Baby et al, 2018 ; Wang et al, 2018 ) which do not necessarily represent their natural biological environment and definitively do not involve complex information management.…”

“…This genocentric paradigm initially allowed researchers to focus on most of the cellular functions. Nevertheless, this approach has become limited as it considers whole genes as single functional units and disregards mechanisms for gene-expression triggering and other putative functions present in non-translated regions of the genome (Baby et al, 2018 ; Wang et al, 2018 ).…”