Immune lag is a major cost of prokaryotic adaptive immunity during viral outbreaks.

Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptive immune systems enable bacteria and archaea to efficiently respond to viral pathogens by creating a genomic record of previous encounters. These systems are broadly distributed across prokaryotic taxa, yet are surprisingly absent in a majority of organisms, suggesting that the benefits of adaptive immunity frequently do not outweigh the costs. Here, combining experiments and models, we show that a delayed immune response which allows viruses to transiently redirect cellular resources to reproduction, which we call 'immune lag', is extremely costly during viral outbreaks, even to completely immune hosts. Critically, the costs of lag are only revealed by examining the early, transient dynamics of a host-virus system occurring immediately after viral challenge. Lag is a basic parameter of microbial defence, relevant to all intracellular, post-infection antiviral defence systems, that has to-date been largely ignored by theoretical and experimental treatments of host-phage systems.

Selective Maintenance of Multiple CRISPR Arrays Across Prokaryotes.

Prokaryotes are under nearly constant attack by viral pathogens. To protect against this threat of infection, bacteria and archaea have evolved a wide array of defense mechanisms, singly and in combination. While immune diversity in a single organism likely reduces the chance of pathogen evolutionary escape, it remains puzzling why many prokaryotes also have multiple, seemingly redundant, copies of the same type of immune system. Here, we focus on the highly flexible CRISPR adaptive immune system, which is present in multiple copies in a surprising 28% of the prokaryotic genomes in RefSeq. We use a comparative genomics approach looking across all prokaryotes to demonstrate that on average, organisms are under selection to maintain more than one CRISPR array. Given this surprising conclusion, we consider several hypotheses concerning the source of selection and include a theoretical analysis of the possibility that a trade-off between memory span and learning speed could select for both "long-term memory" and "short-term memory" CRISPR arrays.