Casposons: mobile genetic elements that gave rise to the CRISPR-Cas adaptation machinery

•Casposons are self-replicating mobile genetic elements found in bacteria and archaea.•Casposase is an active casposon integrase homologous to CRISPR-Cas1.•Casposons gave rise to the adaptation machinery of CRISPR-Cas.•CRISPR repeats and the Leader sequence have evolved from the casposon target site.•Recruitment of Cas2 was crucial for transforming the casposase into Cas1.

A casposon, a member of a distinct superfamily of archaeal and bacterial self-synthesizing transposons that employ a recombinase (casposase) homologous to the Cas1 endonuclease, appears to have given rise to the adaptation module of CRISPR-Cas systems as well as the CRISPR repeats themselves. Comparison of the mechanistic features of the reactions catalyzed by the casposase and the Cas1-Cas2 heterohexamer, the CRISPR integrase, reveals close similarity but also important differences that explain the requirement of Cas2 for integration of short DNA fragments, the CRISPR spacers.

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