Chapter 12 : The CRISPR-Cas Immune System and Genetic Transfers: Reaching an Equilibrium

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In 1987 Ishino et al. ( ) sequenced the alkaline phosphatase isozyme conversion gene (). Downstream of , they observed an array of short repeats (29 nucleotides) separated by nonrepetitive short sequences (spacers) ( ). The terms “CRISPR,” for clustered regularly interspaced short palindromic repeats, and “Cas,” for CRISPR-associated genes, were first coined by Jansen et al. ( ) in 2002 to describe the genetic structure of these loci. The increasing availability of genomic sequences in databases allowed Mojica et al. ( ) to identify CRISPR as a specific family of repeats. Now we know that CRISPR-Cas systems are found in approximately 90% of archaeal and 40% of eubacterial sequenced genomes ( ). In 2005, three groups independently reported similarities between spacer sequences and foreign mobile genetic elements (MGEs) such as phages and plasmids ( ). These observations led to several hypotheses including that CRISPR-Cas systems may play a role in immunity and protect archaeal and bacterial cells from invasion by foreign DNA.

Citation: Samson J, Magadan A, Moineau S. 2015. The CRISPR-Cas Immune System and Genetic Transfers: Reaching an Equilibrium, p 209-218. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0034-2014
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Figure 1

Genetic organization of a type II CRISPR-Cas system and its general steps of action. The CRISPR locus is composed of repeats (black diamonds) interspaced with spacers (red and white rectangles) of similar length. In the vicinity of the CRISPR array, genes (colored arrows) are coding for proteins necessary for the immunity process. During the adaptation step, a repeat and, most importantly, a new spacer (red rectangle) is acquired in the CRISPR locus, usually at the 5′ region. Transcription of the CRISPR locus leads to pre-crRNAs that are processed, leading to short crRNAs. These crRNAs are assembled with Cas protein(s) in ribonucleoprotein complexes that act as surveillance guides looking for matching invading sequences. If the crRNA sequence matches a protospacer found on the foreign and invading nucleic acid molecule and if a PAM (gray box) is present next to the protospacer (for type I and II systems), this leads to the cleavage of the invading molecule (interference step).

Citation: Samson J, Magadan A, Moineau S. 2015. The CRISPR-Cas Immune System and Genetic Transfers: Reaching an Equilibrium, p 209-218. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0034-2014
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Image of Figure 2
Figure 2

Probable action of CRISPR-Cas systems against invading plasmids. (A) Plasmids entering a bacterial cell via natural transformation (free DNA), conjugation (pilus not represented), and transduction (phagemids). Of note, to date, no CRISPR-Cas system has been identified that cleaves ssDNA molecules . However, after their entry in the bacteria, ssDNA are usually transformed into double-stranded DNA molecules (dsDNA) and maintained as plasmids or integrated within the chromosome. If the new dsDNA molecule contains a protospacer matching a crRNA sequence, it will be cleaved by the CRISPR-Cas machinery in a sequence-specific manner. (B) During artificial transformation of the bacterium with heat treatments or electroporation, dsDNA directly enters the cells. Thus, the CRISPR-Cas ribonucleoprotein complexes can directly target these dsDNA molecules to eliminate them. (C) Some CRISPR-Cas systems (type III) cleave RNA molecules. After transcription of plasmid genes, these molecules are silenced by the CRISPR-Cas system, and after a few rounds of bacterial replication, these plasmids may be lost.

Citation: Samson J, Magadan A, Moineau S. 2015. The CRISPR-Cas Immune System and Genetic Transfers: Reaching an Equilibrium, p 209-218. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0034-2014
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