Two of biology’s biggest stories of the past few years just collided with a novel CRISPR-like defence system found within the genome of a giant virus.
The CRISPR-Cas system is an adaptive immune system protecting bacteria from virus attack, that is now being widely used to edit genomes of eukaryotic cells, including humans, leading to exciting research and therapeutic possibilities. Quite separately, the recent discovery of giant viruses with particle sizes and genomes larger than bacteria, that infect amoebae and have their own virus predators called virophages, has thrown a curved ball into the microbiological pond. Now the Marseille-based group of Didier Raoult has shown that the giant mimivirus itself contains the functional equivalents of CRISPR-Cas; as with the bacterial system, the mimivirus captures short DNA sequences from virophages, leading to immunity. “The war between giant viruses and virophages is similar to that between bacteria and viruses,” said Raoult. Although we already know of examples where CRISPR-Cas systems have been acquired by some bacteriophages, this new mimivirus system appears to be a case of convergent evolution, and so is likely to be completely novel.
There is an enormous amount of work to do to understand these fascinating viruses; the biggest one discovered to date, the pandoravirus, has over 2500 genes, a staggering 94% of which have no known function. There is also a furious debate as to how these strange organisms affect our view of the boundary between the living and non-living, and where they fit into the tree of life.
However, the significance of this work for human biologists, is whether this new mimivirus system might bring new tools to the gene editing table. There is doubtless much that is technologically useful to harvest from the thousands of systems we now know to exist in bacteria, but those tend to be evolutionarily related to CRISPR-Cas. With mimiviruses we might have something quite different. Jennifer Doudna, one of the CRISPR-Cas gene editing pioneers pointed out that we wouldn’t know until the biology had been worked out, but said that “the potential for such a system to be harnessed for genetic control is intriguing”.
So watch this space, for surprising developments both in basic biology and in the gene editing toolbox.