The diversity-generating benefits of a prokaryotic adaptive immune system

Abstract

Prokaryotic CRISPR-Cas adaptive immune systems insert spacers derived from viruses and other parasitic DNA elements into CRISPR loci to provide sequence-specific immunity1,2. This frequently results in high within-population spacer diversity3–6, 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 mechanisms7.

Immigration of susceptible hosts triggers the evolution of alternative parasite defence strategies

“…In the low-migration treatment, phage persisted in two out of six replicate experiments (figure 1a), and at high immigration (10% immigration), phage persisted in four out of six replicates (figure 1b). In the parallel experiment that lacked naive host immigration, phage went extinct in all replicates [24]. Hence, high naive host immigration significantly reduced phage extinction (one-tailed Fisher's exact test, p ¼ 0.03), causing an increase in the force of infection.…”

“…However, we detected no difference in resistance of individual clones from 3 dpi against the contemporary or future phage population (figure 4a), and bacteria from 11 dpi were equally resistant to phage from 3 and 11 dpi ( figure 4b) (F 1,19 ¼ 0.1312, p ¼ 0.7212). The lack of detectable coevolution is presumably because of the high level of CRISPR spacer diversity that naturally evolves in P. aeruginosa upon infection with DMS3vir, which has previously been shown to constrain the evolution of escape phage in the absence of immigration [24].…”

“…BIM-4sp carries multiple spacers that target phage DMS3vir and the phage can, therefore, not evolve to overcome CRISPR immunity [24,27], hence excluding the second, coevolutionary explanation as a confounding factor during this experiment. Competition was performed in the presence of phage DMS3vir and in the presence or absence of naive host immigration.…”

“…R. Soc. B 283: 20160721 evolution of CRISPR-Cas-mediated immunity [24]. While parasites and hosts often go extinct locally, it is frequently observed that they can persist in structured environments where hosts and parasites migrate between subpopulations [3].…”

“…Recently, we demonstrated that evolution of CRISPRCas-mediated immunity in P. aeruginosa results in rapid phage extinction [24]. In this study, we examine the impact of naive host immigration to a population of P. aeruginosa that use CRISPR-Cas to protect against phage infection.…”