Diversity, classification and evolution of CRISPR-Cas systems

Diversity, classification and evolution of CRISPR-Cas systems

2017 June | Eugene V. Koonin, Kira S. Makarova, and Feng Zhang
CRISPR-Cas systems in bacteria and archaea exhibit remarkable diversity in protein composition, effector complex structure, genome locus architecture, and mechanisms of adaptation, pre-crRNA processing, and interference. These systems are classified into two main classes: Class 1, which includes multi-subunit effector complexes, and Class 2, which consists of single-protein effector modules. Recent studies have identified two new types (VI and V) within Class 2, with type VI being the first to exclusively target RNA. Comparative analysis suggests that Class 2 systems evolved from mobile genetic elements on multiple occasions. Class 2 systems include type II, which uses Cas9 as the effector endonuclease, and type V, which includes Cpf1. Type VI systems, such as Cas13a and Cas13b, are dedicated RNA-targeting systems that cleave RNA in a non-sequence-specific manner. These systems are regulated by accessory proteins and can induce cellular toxicity, suggesting a link between immunity and dormancy or programmed cell death. The pre-crRNA processing in Class 2 systems is carried out by the effector proteins themselves, with some systems, like type V-B, requiring tracrRNA for maturation and target cleavage. The evolution of CRISPR-Cas systems is closely linked to mobile genetic elements, such as Casposons, which contribute to the adaptation module. The effector modules of Class 2 systems have evolved independently from transposon genes, with some containing HEPN domains for target cleavage. The diversity of CRISPR-Cas systems has led to the discovery of new effector proteins and mechanisms, including RNA-targeting systems and the use of RNA for adaptation. These findings highlight the complexity and adaptability of CRISPR-Cas systems, which play a crucial role in bacterial and archaeal immunity. The classification of CRISPR-Cas systems continues to evolve, reflecting the dynamic nature of these systems in response to viral threats.CRISPR-Cas systems in bacteria and archaea exhibit remarkable diversity in protein composition, effector complex structure, genome locus architecture, and mechanisms of adaptation, pre-crRNA processing, and interference. These systems are classified into two main classes: Class 1, which includes multi-subunit effector complexes, and Class 2, which consists of single-protein effector modules. Recent studies have identified two new types (VI and V) within Class 2, with type VI being the first to exclusively target RNA. Comparative analysis suggests that Class 2 systems evolved from mobile genetic elements on multiple occasions. Class 2 systems include type II, which uses Cas9 as the effector endonuclease, and type V, which includes Cpf1. Type VI systems, such as Cas13a and Cas13b, are dedicated RNA-targeting systems that cleave RNA in a non-sequence-specific manner. These systems are regulated by accessory proteins and can induce cellular toxicity, suggesting a link between immunity and dormancy or programmed cell death. The pre-crRNA processing in Class 2 systems is carried out by the effector proteins themselves, with some systems, like type V-B, requiring tracrRNA for maturation and target cleavage. The evolution of CRISPR-Cas systems is closely linked to mobile genetic elements, such as Casposons, which contribute to the adaptation module. The effector modules of Class 2 systems have evolved independently from transposon genes, with some containing HEPN domains for target cleavage. The diversity of CRISPR-Cas systems has led to the discovery of new effector proteins and mechanisms, including RNA-targeting systems and the use of RNA for adaptation. These findings highlight the complexity and adaptability of CRISPR-Cas systems, which play a crucial role in bacterial and archaeal immunity. The classification of CRISPR-Cas systems continues to evolve, reflecting the dynamic nature of these systems in response to viral threats.
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[slides and audio] Diversity%2C classification and evolution of CRISPR-Cas systems.