The diversity-generating benefits of a prokaryotic adaptive immune system

Published onlineJOURNAL ARTICLEProkaryotic CRISPR-Cas adaptive immune systems insert spacers derived from viruses and other parasitic DNA elements into CRISPR loci to provide sequence-specific immunity. This frequently results in high within-population spacer diversity, 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.S.v.H. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 660039. E.R.W. received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under Research Executive Agency grant agreement number 327606. E.R.W., A.B. and M.B. also acknowledge the Natural Environment Research Council, the Biotechnology and Biological Sciences Research Council, the Royal Society, the Leverhulme Trust, the Wellcome Trust and the AXA research fund for funding. J.M.B.-D. was supported by the University of California San Francisco Program for Breakthrough in Biomedical Research, the Sandler Foundation, and a National Institutes of Health Director’s Early Independence Award (DP5-OD021344). H.C. was funded by the Erasmus+ programme (European Union), the Explora’Sup programme (Région Rhône-Alpes) and the Centre Régional des Œuvres Universitaires et Scolaires (CROUS; French State)

Data from: Host diversity limits the evolution of parasite local adaptation

Specificity in the interactions between hosts and their parasites can lead to local adaptation. However, the degree of local adaptation is predicted to depend upon the diversity of resistance alleles within the host population; increasing host diversity should decrease mean parasite infectivity and hence reduce local adaptation. In this study, we empirically test this prediction using the highly specific interactions between bacteria with clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) immunity and their bacteriophage. Bacteria acquire immunity to phage by incorporating a phage-derived spacer sequence into CRISPR loci on the host genome, and phage can escape the CRISPR-mediated immunity of a specific clone by mutating the targeted sequence. We found that high levels of CRISPR allele diversity that naturally evolve in host populations exposed to phage (because each bacterial clone captures a unique phage-derived sequence) prevents phage from becoming locally adapted. By manipulating the number of CRISPR alleles in the host population, we show that phage can become locally adapted to their bacterial hosts but only when CRISPR allele diversity is low

Parasite local adaptation on host populations of increasing genetic diversity

This file contains the raw bacteria and phage counts and average local adaptation scores for 5-day coevolution experiments in which phage were added to populations of Pseudomonas aeruginosa with increasing levels of CRISPR spacer diversity. The goal was to measure parasite (phage) location adaptation on host populations (Pesudomonas aeruginosa) with varying levels of resistance alleles (CRISPR spacers) to measure the effects of host diversity on parasite local adaptation