The size of the immune repertoire of bacteria

Abstract

Some bacteria and archaea possess an immune system, based on the CRISPR-Cas mechanism, that confers adaptive immunity against viruses. In such species, individual prokaryotes maintain cassettes of viral DNA elements called spacers as a memory of past infections. Typically, the cassettes contain several dozen expressed spacers. Given that bacteria can have very large genomes and since having more spacers should confer a better memory, it is puzzling that so little genetic space would be devoted by prokaryotes to their adaptive immune systems. Here, assuming that CRISPR functions as a long-term memory-based defense against a diverse landscape of viral species, we identify a fundamental tradeoff between the amount of immune memory and effectiveness of response to a given threat. This tradeoff implies an optimal size for the prokaryotic immune repertoire in the observational range.

Heterologous autoimmunity and prokaryotic immune defense

“…Many theoretical studies of adaptive immunity in both prokaryotes [8,[37][38][39][40][41][42][43][44] and vertebrates [52][53][54][55] consider detailed dynamical models of evolving immune repertoires. For prokaryotes, such dynamical models can be regarded as describing the role of CRISPR-Cas as a shortterm memory for defense against a co-evolving phage [56]. Studying adaptive immunity in this way requires detailed knowledge of the parameters controlling the dynamics, many of which are not well-characterized experimentally.…”

“…Maintaining a broad spacer repertoire confers resistance against many phages and possible escape mutants [6]. However, there are constitutive costs associated with Cas protein expression [7], and diminishing returns of broad defense due to finite Cas protein copy numbers [8,9]. In addition, CRISPR-Cas systems can prevent horizontal transfer of beneficial mobile genetic elements [10,11].…”

Optimal evolutionary decision-making to store immune memory

“…Our statistical framework, on the other hand, aims to characterize high-level features for an optimal memory strategy, without relying on mechanistic details of the underlying process, some of which are at least partially unknown [24,25]. In the case of the immune system, statistical models have provided an intuition for how an immune repertoire should be organized to optimally counter diverse pathogens [19,[26][27][28][29]. In a similar fashion, optimal memory strategies identified by our model provide a baseline to gauge the performance of real immune systems in storing and utilizing memory.…”

Transcription termination and antitermination of bacterial CRISPR arrays

“…CRISPR arrays can be expanded by acquisition of new spacer/repeat elements at one end of the array, in a process known as adaptation. The ability to become immune to newly encountered invaders is presumably a strong selective pressure that promotes adaptation ( Bradde et al, 2020 ; Martynov et al, 2017 ), although shorter CRISPR arrays appear to be strongly favored in bacteria ( Weissman et al, 2018 ). Little is known about factors that negatively influence CRISPR array length.…”

“…Little is known about factors that negatively influence CRISPR array length. It has been hypothesized that increased array length is selected against because of the potential for individual crRNAs to become less effective as the effector complex is diluted among more crRNA variants ( Bradde et al, 2020 ; Martynov et al, 2017 ; Rao et al, 2017 ). The diversity of potential invaders and the mutation frequency of invaders have also been proposed to impose selective pressure on array length ( Martynov et al, 2017 ).…”