ArticleBMC evolutionary biology2017
Phylogenomics of Cas4 family nucleases.
Article in BMC evolutionary biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
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- Discovery of CRISPR-Cas12a clades using a large language model.Nature communications · 2025Article
- Cyanobacterial Argonautes and Cas4 family nucleases cooperate to interfere with invading DNA.Molecular cell · 2025Article
- Functional insights into Solo-Cas4 inmicroLife · 2025Article
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- Diverse viral cas genes antagonize CRISPR immunity.Nature · 2024Article
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- Genome sequence and characterization of a novel Pseudomonas putida phage, MiCath.Scientific reports · 2023Article
- Cas4/1 dual nuclease activities enable prespacer maturation and directional integration in a type I-G CRISPR-Cas system.bioRxiv : the preprint server for biology · 2023Article
- Genome expansion by a CRISPR trimmer-integrase.Nature · 2023Article
- The biology and type I/III hybrid nature of type I-D CRISPR-Cas systems.The Biochemical journal · 2023Review
- In Silico Approaches for Prediction of Anti-CRISPR Proteins.Journal of molecular biology · 2023Review
- CRISPR-Cas systems feature and targeting phages diversity inFrontiers in microbiology · 2023Article
- CRISPR-Cas systems: role in cellular processes beyond adaptive immunity.Folia microbiologica · 2022Review
- PAM binding ensures orientational integration during Cas4-Cas1-Cas2-mediated CRISPR adaptation.Molecular cell · 2022Article
- Adaptation by Type V-A and V-B CRISPR-Cas Systems Demonstrates Conserved Protospacer Selection Mechanisms Between Diverse CRISPR-Cas Types.The CRISPR journal · 2022Article
- Sulfur cycling and host-virus interactions in Aquificales-dominated biofilms from Yellowstone's hottest ecosystems.The ISME journal · 2022Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe Cas4 family endonuclease is a component of the adaptation module in many variants of CRISPR-Cas adaptive immunity systems. Unlike most of the other Cas proteins, Cas4 is often encoded outside CRISPR-cas loci (solo-Cas4) and is also found in mobile genetic elements (MGE-Cas4).
resultsAs part of our ongoing investigation of CRISPR-Cas evolution, we explored the phylogenomics of the Cas4 family. About 90% of the archaeal genomes encode Cas4 compared to only about 20% of the bacterial genomes. Many archaea encode both the CRISPR-associated form (CAS-Cas4) and solo-Cas4, whereas in bacteria, this combination is extremely rare. The solo-cas4 genes are over-represented in environmental bacteria and archaea with small genomes that typically lack CRISPR-Cas, suggesting that Cas4 could perform uncharacterized defense or repair functions in these microbes. Phylogenomic analysis indicates that both the CRISPR-associated cas4 genes are often transferred horizontally but almost exclusively, as part of the adaptation module. The evolutionary integrity of the adaptation module sharply contrasts the rampant shuffling of CRISPR-cas modules whereby a given variant of the adaptation module can combine with virtually any effector module. The solo-cas4 genes evolve primarily via vertical inheritance and are subject only to occasional horizontal transfer. The selection pressure on cas4 genes does not substantially differ between CAS-Cas4 and solo-cas4, and is close to the genomic median. Thus, cas4 genes, similarly to cas1 and cas2, evolve similarly to 'regular' microbial genes involved in various cellular functions, showing no evidence of direct involvement in virus-host arms races. A notable feature of the Cas4 family evolution is the frequent recruitment of cas4 genes by various mobile genetic elements (MGE), particularly, archaeal viruses. The functions of Cas4 in these elements are unknown and potentially might involve anti-defense roles.
conclusionsUnlike most of the other Cas proteins, Cas4 family members are as often encoded by stand-alone genes as they are incorporated in CRISPR-Cas systems. In addition, cas4 genes were repeatedly recruited by MGE, perhaps, for anti-defense functions. Experimental characterization of the solo and MGE-encoded Cas4 nucleases is expected to reveal currently uncharacterized defense and anti-defense systems and their interactions with CRISPR-Cas systems.
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