I think of CRISPR as being a subset of “adaptive” bacterial systems that promote host
survival. These adaptive systems are macromolecular systems that enhance host survival
in a myriad of ways: by destroying foreign DNA, by mediating horizontal gene transfer,
or even by altering host metabolism, among many other diverse functions. In this sense,
CRISPR represents just the tip of the iceberg; there are likely many unexplored and
uncharacterized adaptive systems that would be practically useful for genomic manipulation.
Therefore, identification and characterization of functionally useful adaptive systems
is a major bottleneck in the development of new technologies. Bacterial genomes are
fast-evolving. Furthermore, sampling of bacterial genomes is sparse compared to the
vast diversity of bacterial species. All of this makes computational identification
of novel adaptive systems challenging. High-throughput screens are useful if a suitable
assay can be identified. Alternatively, common mechanistic principles can be obtained
using biochemical and structural characterization, which could guide identification
of adaptive systems.
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