ABSTRACT
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 21% of the prokaryotic genomes in RefSeq. We use a comparative genomics approach looking across all prokaryotes to demonstrate that having more than one CRISPR system confers a selective advantage to the organism, on average. This adaptive signature appears to be a function of more subtle diversity between the CRISPR systems rather than their multiplicity alone. We go on to develop a mathematical model of CRISPR immune memory turnover to show how a tradeoff between memory span and learning speed can lead to selection for “long-term memory” and “short-term memory” arrays.
Significance Statement Many viruses infect bacteria and archaea. To protect themselves, these microbes employ a variety of defense mechanisms. Surprisingly, many microbes have multiple copies of the same type of defense system encoded on their genome. We determine whether this apparent redundancy of immunity is adaptive, and why it would be so. Specifically, we examine the CRISPR immune system, which allows microbes to store immune “memories” of past infections and use these memories to fight future infections. Using publicly available genomic data we show that having two CRISPR systems is adaptive, on average. We also build a theoretical model indicating it is adaptive for microbes to have CRISPR systems specializing as both “short-term” and “long-term” memory for rapid response and reliable storage.