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      Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire

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          Abstract

          All cellular life forms are afflicted by diverse genetic parasites, including viruses and other types of mobile genetic elements (MGEs), and have evolved multiple, diverse defence systems that protect them from MGE assault via different mechanisms. Here, we provide our perspectives on how recent evidence points to tight evolutionary connections between MGEs and defence systems that reach far beyond the proverbial arms race. Defence systems incur a fitness cost for the hosts; therefore, at least in prokaryotes, horizontal mobility of defence systems, mediated primarily by MGEs, is essential for their persistence. Moreover, defence systems themselves possess certain features of selfish elements. Common components of MGEs, such as site-specific nucleases, are 'guns for hire' that can also function as parts of defence mechanisms and are often shuttled between MGEs and defence systems. Thus, evolutionary and molecular factors converge to mould the multifaceted, inextricable connection between MGEs and anti-MGE defence systems.

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          Most cited references108

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          Diversity and evolution of class 2 CRISPR–Cas systems

          Class 2 CRISPR–Cas systems are characterized by effector modules that consist of a single multidomain protein. In this Analysis, using a computational pipeline, the authors discover three novel families of class 2 effectors that correspond to three new CRISPR–Cas subtypes and present a comprehensive census of class 2 systems that are encoded in complete and draft bacterial and archaeal genomes.
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            Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems.

            Adaptive immunity had been long thought of as an exclusive feature of animals. However, the discovery of the CRISPR-Cas defense system, present in almost half of prokaryotic genomes, proves otherwise. Because of the everlasting parasite-host arms race, CRISPR-Cas has rapidly evolved through horizontal transfer of complete loci or individual modules, resulting in extreme structural and functional diversity. CRISPR-Cas systems are divided into two distinct classes that each consist of three types and multiple subtypes. We discuss recent advances in CRISPR-Cas research that reveal elaborate molecular mechanisms and provide for a plausible scenario of CRISPR-Cas evolution. We also briefly describe the latest developments of a wide range of CRISPR-based applications.
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              Mechanisms of site-specific recombination.

              Integration, excision, and inversion of defined DNA segments commonly occur through site-specific recombination, a process of DNA breakage and reunion that requires no DNA synthesis or high-energy cofactor. Virtually all identified site-specific recombinases fall into one of just two families, the tyrosine recombinases and the serine recombinases, named after the amino acid residue that forms a covalent protein-DNA linkage in the reaction intermediate. Their recombination mechanisms are distinctly different. Tyrosine recombinases break and rejoin single strands in pairs to form a Holliday junction intermediate. By contrast, serine recombinases cut all strands in advance of strand exchange and religation. Many natural systems of site-specific recombination impose sophisticated regulatory mechanisms on the basic recombinational process to favor one particular outcome of recombination over another (for example, excision over inversion or deletion). Details of the site-specific recombination processes have been revealed by recent structural and biochemical studies of members of both families.
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                Author and article information

                Journal
                Nature Reviews Genetics
                Nat Rev Genet
                Springer Science and Business Media LLC
                1471-0056
                1471-0064
                October 14 2019
                Article
                10.1038/s41576-019-0172-9
                31611667
                9a67940e-b634-43d7-9f37-b53739bde447
                © 2019

                http://www.springer.com/tdm

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