Competition and coevolution drive the evolution and the diversification of CRISPR immunity

Abstract

The diversity of resistance fuels host adaptation to infectious diseases and challenges the ability of pathogens to exploit host populations [1–3]. Yet, how this host diversity evolves over time remains unclear because it depends on the interplay between intraspecific competition and co-evolution with pathogens. Here we study the effect of a coevolving phage population on the diversification of bacterial CRISPR immunity across space and time. We demonstrate that the negative-frequency-dependent selection generated by coevolution is a powerful force that maintains host resistance diversity and selects for new resistance mutations in the host. We also find that host evolution is driven by asymmetries in competitive abilities among different host genotypes. Even if the fittest host genotypes are targeted preferentially by the evolving phages they often escape extinctions through the acquisition of new CRISPR immunity. Together, these fluctuating selective pressures maintain diversity, but not by preserving the pre-existing host composition. Instead, we repeatedly observe the introduction of new resistance genotypes stemming from the fittest hosts in each population. These results highlight the importance of competition on the transient dynamics of host-pathogen coevolution.

Extensive diversity and rapid turnover of phage defense repertoires in cheese-associated bacterial communities

“…18). This observation is in contrast to what has been observed in laboratory studies of phage-bacteria coevolution (36,45) or in cases of chronic phage infections in S. thermophilus (31), where multiple spacers targeting the same vOTU were often found to be integrated into the CRISPR array.…”

“…If the spacers have any ecological relevance (36, 37), one would expect to find a positive correlation between the abundances of phages and their matching spacer sequences. To quantify both spacer and phage (i.e.…”

Dynamics of immune memory and learning in bacterial communities

“…What determines clonal diversity? Many factors that correlate with transient diversity have been experimentally identified, such as phage extinction and slower phage evolution at high bacterial spacer diversity [25, 28] and maintenance of a diverse bacterial population when exposed to diverse phages [24, 27, 31, 75], but a conceptual framework to understand emergent diversity has remained elusive. For instance, while initial high spacer diversity puts low-diversity phage populations under intense pressure to the point of driving them extinct [25, 28], is the same true for emergent bacterial diversity after an extended period of coexistence?…”

“…A similar time-shift calculation using sequence data was performed by Guillemet et al . [31]; they approached the question from the phage perspective and found that phages are most infectious against bacteria from the past and least infectious against bacteria from the future. Our results show that powerful insights into the dynamical immune state of a population can be obtained from sequencing data without explicitly performing time shift experiments.…”

“…The kinetics and interactions of phages and bacteria with CRISPR systems have been the subject of numerous experiments [25, 27, 28, 29, 30, 31]. Some themes have emerged from experimental studies of CRISPR immunity: (a) high spacer diversity relative to phage diversity increases the likelihood of phage extinction [25, 28, 31], (b) bacteria become more immune to phages over time [32, 33, 27, 34], and (c) phages readily gain mutations [35, 23, 36, 37, 38, 34, 31, 39] and sometimes genome rearrangements [24] to escape CRISPR targeting. Explorations of CRISPR immunity in natural environments have also documented ongoing spacer acquisition and phage escape mutations [35, 39].…”