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Resistance and tolerance to foreign elements by prokaryotic immune systems — curating the genome

Abstract

To engage in adaptive symbioses or genetic exchange, organisms must interact with foreign, non-self elements despite the risks of predation and parasitism. By surveying the interface between self and non-self, immune systems can help ensure the benevolence of these interactions without isolating their hosts altogether. In this Essay, we examine prokaryotic restriction–modification and CRISPR–Cas (clustered, regularly interspaced palindromic repeat–CRISPR-associated proteins) activities and discuss their analogy to mammalian immune pathways. We further explain how their capacities for resistance and tolerance are optimized to reduce parasitism and immunopathology during encounters with non-self.

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Figure 1: Genome evolution resulting from vertical or horizontal transmission of DNA.
Figure 2: Prokaryotic analogues of innate and adaptive immunity.
Figure 3: Tolerance of foreign DNA during prokaryotic nucleic acid surveillance.

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Acknowledgements

The authors would like to thank D. Mucida and P. M. Nussenzweig at The Rockefeller University for critical discussion and corrections to the manuscript. L.A.M is supported by the Searle Scholars Program, Rita Allen Scholars Program, an Irma T. Hirschl Award, a Sinsheimer Foundation Award and a US National Institutes of Health (NIH) Director's New Innovator Award (1DP2AI104556-01).

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Correspondence to Gregory W. Goldberg or Luciano A. Marraffini.

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Goldberg, G., Marraffini, L. Resistance and tolerance to foreign elements by prokaryotic immune systems — curating the genome. Nat Rev Immunol 15, 717–724 (2015). https://doi.org/10.1038/nri3910

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