CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers.

Franziska Wimmer,Chase L Beisel

doi:10.3389/fmicb.2019.03078

Abstract

CRISPR-Cas immune systems in bacteria and archaea record prior infections as spacers within each system’s CRISPR arrays. Spacers are normally derived from invasive genetic material and direct the immune system to complementary targets as part of future infections. However, not all spacers appear to be derived from foreign genetic material and instead can originate from the host genome. Their presence poses a paradox, as self-targeting spacers would be expected to induce an autoimmune response and cell death. In this review, we discuss the known frequency of self-targeting spacers in natural CRISPR-Cas systems, how these spacers can be incorporated into CRISPR arrays, and how the host can evade lethal attack. We also discuss how self-targeting spacers can become the basis for alternative functions performed by CRISPR-Cas systems that extend beyond adaptive immunity. Overall, the acquisition of genome-targeting spacers poses a substantial risk but can aid in the host’s evolution and potentially lead to or support new functionalities.

Highlights

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems represent highly diverse adaptive immune systems found in many bacteria and most archaea (Barrangou et al, 2007; Sorek et al, 2013; Koonin et al, 2017)
We address the known distribution of self-targeting spacers in sequenced CRISPR-Cas systems
We report some of the beneficial functions that have been associated with the self-targeting spacers that can imbue CRISPR-Cas systems with functionalities that extend beyond adaptive immunity

Summary

Introduction

CRISPR-Cas systems represent highly diverse adaptive immune systems found in many bacteria and most archaea (Barrangou et al, 2007; Sorek et al, 2013; Koonin et al, 2017). Naïve acquisition by different types of CRISPR-Cas systems can lead to the incorporation of self-targeting spacers, foreign genetic material is the predominant source of spacers. Self-targeting spacers have been found in three strains encoding a RT as part of their type III CRISPR-Cas systems (Silas et al, 2017; Zhang et al, 2018).

Results

Conclusion