It is unclear how important CRISPR-Cas systems are for protecting natural populations of bacteria against infections by mobile genetic elements

Edze R Westra,Bruce R Levin

doi:10.1073/pnas.1915966117

Edze R Westra, Bruce R Levin

Open Access

https://doi.org/10.1073/pnas.1915966117

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Abstract

Articles on CRISPR commonly open with some variant of the phrase “these short palindromic repeats and their associated endonucleases (Cas) are an adaptive immune system that exists to protect bacteria and archaea from viruses and infections with other mobile genetic elements.” There is an abundance of genomic data consistent with the hypothesis that CRISPR plays this role in natural populations of bacteria and archaea, and experimental demonstrations with a few species of bacteria and their phage and plasmids show that CRISPR-Cas systems can play this role in vitro. Not at all clear are the ubiquity, magnitude, and nature of the contribution of CRISPR-Cas systems to the ecology and evolution of natural populations of microbes and the strength of selection mediated by different types of phage and plasmids to the evolution and maintenance of CRISPR-Cas systems. In this perspective, with the aid of heuristic mathematical–computer simulation models, we explore the a priori conditions under which exposure to lytic and temperate phage and conjugative plasmids will select for and maintain CRISPR-Cas systems in populations of bacteria and archaea. We review the existing literature addressing these ecological and evolutionary questions and highlight the experimental and other evidence needed to fully understand the conditions responsible for the evolution and maintenance of CRISPR-Cas systems and the contribution of these systems to the ecology and evolution of bacteria, archaea, and the mobile genetic elements that infect them.

Highlights

In 1987, a study by Ishino and colleagues [1] aimed at analyzing the nucleotide sequence of the iap gene in Escherichia coli serendipitously led to the first-ever description of a Clustered regularly interspaced short palindrome repeats (CRISPRs) array
There is an abundance of genomic data consistent with the hypothesis that CRISPR plays this role in natural populations of bacteria and archaea, and experimental demonstrations with a few species of bacteria and their phage and plasmids show that CRISPR-Cas systems can play this role in vitro
The original idea that CRISPR-Cas is an adaptive immune system came from observations that sequences in CRISPR arrays on the chromosomes of bacteria match those of phage and other foreign genetic aEnvironment and Sustainability Institute, Biosciences, University of Exeter, Penryn, TR10 9FE Cornwall, United Kingdom; and bDepartment of Biology, Emory University, Atlanta, GA 30307 Author contributions: B.R.L. carried out the mathematical modeling; and E.R.W. and B.R.L. wrote the paper

Summary

Introduction

In 1987, a study by Ishino and colleagues [1] aimed at analyzing the nucleotide sequence of the iap (isozyme-converting alkaline phosphatase) gene in Escherichia coli serendipitously led to the first-ever description of a CRISPR array. If CRISPR-Cas is commonly important for protecting populations of microbes from phage and preventing the acquisition of MGEs, there should be no trouble detecting (in the laboratory or in nature) CRISPR-Cas–encoding bacteria and archaea that acquire spacers from novel sources of infectious DNAs to become immune to those infections.

Results

Conclusion