Universal genome cutters: from selfish genetic elements to antivirus defence and genome editing tools

system goes through a far more complex route.The CRISPR defence response starts with the adaptation step whereby foreign (e.g.bacteriophage) DNA is recognized by the Cas1-Cas2 protein complex after which Cas1, a transposase-like enzyme, cuts out a piece of DNA and with the help of the microbial repair machinery inserts it into the CRISPR array.The CRISPR locus including the phage-specific spacers is then transcribed, the long transcript is processed into mature CRISPR (cr) RNAs consisting of the spacer (guide) and parts of the adjacent repeats, the crRNA is loaded onto the effector nuclease, which in at least some CRISPR variants also participates in the crRNA maturation, and the latter cleaves the cognate region of the target (Figure 1).Once this mechanism of the CRISPR-Cas function in microbial immunity was deciphered, the startling realization was that this system embodies the Lamarckian evolutionary scenario 3 .Indeed, CRISPR-Cas mediates direct adaptation of an organism to an environmental factor (specifically, resistance to a virus) through directed, stably inheritable modification of the host genome.The key problem for such a mechanism, as for many defence strategies, is self-versus non-selfdiscrimination, and it is still far from being clear how good different variants of CRISPR-Cas are at recognizing invading foreign DNA.Some have been reported to efficiently recognize foreign DNA, in particular, small genomes of viruses and plasmids thanks to their high replication activity, reaffirming the adaptive, Lamarckian character of microbial adaptive immunity.Surprisingly, however, other CRISPR-Cas variants seem to incorporate spacers indiscriminately which often leads to autoimmunity.In this case, the operation of the system involves selection of the fittest variants (those that contain a virus-specific spacer) and appears to be more Darwinian than Lamarckian.Thus, even fundamental aspects of CRISPR-induced genome evolution appear to differ between different types of these adaptive