In the publication that provided the first evidence of CRISPR-Cas as an adaptive immune system [Barrangou, R., et al. (2007). Science. 315:1709–1712], the authors state that CRISPR-Cas “provides a historical perspective of phage exposure, as well as a predictive tool for phage sensitivity.” Explain how this is true using what you know about the CRISPR locus.

Verified step by step guidance

1. Step 1: Understand the structure of the CRISPR locus, which consists of short, repetitive DNA sequences (repeats) interspersed with unique sequences called spacers. Each spacer corresponds to a fragment of DNA derived from a previous phage (virus) infection.
2. Step 2: Recognize that when a bacterium survives a phage infection, it incorporates a new spacer sequence into its CRISPR locus, effectively creating a genetic record or 'memory' of that specific phage exposure.
3. Step 3: Realize that this historical record allows the bacterium to recognize and target the same or similar phages in future encounters by producing CRISPR RNAs (crRNAs) that guide Cas proteins to the matching phage DNA for cleavage and destruction.
4. Step 4: Understand that by analyzing the spacer sequences within the CRISPR locus, scientists can infer which phages the bacterium or its ancestors have been exposed to, providing a historical perspective of phage exposure.
5. Step 5: Additionally, since the presence of specific spacers predicts the bacterium's ability to recognize and defend against corresponding phages, the CRISPR locus serves as a predictive tool for phage sensitivity or resistance.

Key Concepts

CRISPR-Cas Adaptive Immune System

CRISPR-Cas is a bacterial defense mechanism that captures snippets of DNA from invading viruses (phages) and incorporates them into the CRISPR locus as spacers. These spacers serve as a genetic memory, allowing the bacteria to recognize and target the same phages during future infections, thus providing adaptive immunity.

CRISPR Locus Structure and Function

The CRISPR locus consists of repeating DNA sequences interspersed with unique spacer sequences derived from past phage infections. This arrangement records a chronological history of phage exposure, enabling the bacterial cell to transcribe RNA guides that direct Cas proteins to matching viral DNA for cleavage.

Phage Sensitivity Prediction via Spacer Matching

By analyzing the spacer sequences within the CRISPR locus, scientists can predict which phages a bacterium is resistant to, as spacers correspond to previously encountered viruses. If a phage’s DNA matches a spacer, the bacterium can mount an immune response, making the CRISPR locus a predictive tool for phage sensitivity.