Résumé
Population-level spacer diversity is a key fitness determinant of CRISPR-Cas adaptive immune systems because it limits the emergence of escape virus.
Diversity in CRISPR-Cas immunity
The CRISPR-Cas adaptive immune system of prokaryotes uses spacer sequences derived from viruses and other invading mobile genetic elements to target and destroy these elements in a sequence-specific manner. As a result, spacer diversity is often high in bacterial populations, but its importance has been unclear as it has been proposed that viruses overcome spacer diversity by evolving escape mutations. Using experimental evolution to track the co-evolution of a
Pseudomonas aeruginosa
bacteriophage with its host bacterium, Edze Westra and colleagues demonstrate that a high level of spacer diversity actually drives the virus population to extinction, as a result of the synergy between spacer diversity and the high specificity of viral infection. These data reveal that high spacer diversity is key to the success of CRISPR-Cas immunity as it limits the ability of viruses to escape.
Prokaryotic CRISPR-Cas adaptive immune systems insert spacers derived from viruses and other parasitic DNA elements into CRISPR loci to provide sequence-specific immunity
1
,
2
. This frequently results in high within-population spacer diversity
3
,
4
,
5
,
6
, but it is unclear if and why this is important. Here we show that, as a result of this spacer diversity, viruses can no longer evolve to overcome CRISPR-Cas by point mutation, which results in rapid virus extinction. This effect arises from synergy between spacer diversity and the high specificity of infection, which greatly increases overall population resistance. We propose that the resulting short-lived nature of CRISPR-dependent bacteria–virus coevolution has provided strong selection for the evolution of sophisticated virus-encoded anti-CRISPR mechanisms
7
.