When Homing Endonuclease Meets Transposon: The OMEGA System
Simple Summary The CRISPR-Cas9 and CRISPR-Cas12 systems recognize target DNA through base pairing with their guide RNAs, revolutionarily simplifying the design of DNA endonucleases with novel target-sequence specificity for genome editing and gene therapy, compared with endonucleases that rely on protein-based target recognition. The OMEGA (Obligate Mobile Element-Guided Activity) system, considered a precursor to Cas12, and likely to Cas9, in the CRISPR-Cas system, is widely present in the three domains of life as an auxiliary component of transposons. Recent studies have shown that the OMEGA system cleaves the site from which a transposon was excised, thereby inducing transposon restoration via gene conversion. It is now evident that the OMEGA system acts selfishly as a homing endonuclease. This article will focus on the selfish behavior of classical homing endonucleases and the OMEGA system, and discuss how it has evolved, been maintained, and adapted to new genomic environments.