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When Homing Endonuclease Meets Transposon: The OMEGA System.

Sequence-specific DNA endonucleases have made significant contributions to biology, biotechnology, and medicine; restriction enzymes and homing endonucleases are among classic examples. The demonstration of programmable genome editing using Cas9 in the CRISPR-Cas system, in which the target DNA sequence is recognized by base pairing with a guide RNA, revolutionized the field of genome engineering, making target selection more flexible and convenient. The OMEGA (Obligate Mobile Element-Guided Activity) system, considered a precursor to Cas12, and likely to Cas9, in the CRISPR-Cas system, is an RNA-guided DNA endonuclease composed of a TnpB, IscB, IsrB, or Fanzor protein, and a structural RNA designated reRNA or ωRNA. The OMEGA system is present in the three domains of life as an auxiliary component of transposons. The OMEGA system cuts DNA in an allele from which a transposon is excised and triggers recombination to reinstate the transposon at the same position. This "transposon restorative homing" redefines the OMEGA system as a homing endonuclease. In this review, the selfish aspects of the OMEGA system are discussed in the historical context of homing endonuclease research.

Cas12

An Alternative Self-Splicing Intron Lifecycle Revealed by Dynamic Intron Turnover in Epichloë Endophyte Mitochondrial Genomes.

Self-splicing group I and II introns are selfish genetic elements that are widely yet patchily distributed across the tree of life. Their selfish behavior comes from super-Mendelian inheritance behaviors, collectively called "homing", which allow them to rapidly spread within populations to the specific genomic sites they home into. Observations of self-splicing intron evolutionary dynamics have led to the formulation of an intron "lifecycle" model where, once fixed in a population, the introns lose selection for homing and undergo an extensive period of degradation until their eventual loss. Here, we find that self-splicing introns are common in the mitochondrial genomes of Epichloë species, endophytic fungi that live in symbioses with grasses. However, these introns show substantial intron presence-absence polymorphism, with our analyses suggesting that these result from a combination of vertical intron inheritance coupled with multiple invasion and loss events over the course of Epichloë evolution. Surprisingly, we find little evidence for the extensive intron degradation expected under the existing intron lifecycle model. Instead, these introns in Epichloë appear to be lost soon after fixation, suggesting that Epichloë self-splicing introns have a different lifecycle. However, rapid intron loss alone cannot explain our results, indicating that additional factors, such as the evolution of homing suppressors, also contribute to Epichloë self-splicing intron dynamics. This work shows that self-splicing introns have more diverse evolutionary dynamics than previously appreciated.

Introns