Which component of the CRISPR/Cas9 gene editing system is NOT of natural origin?
- (A)
CAS9 protein
- (B)
CRISPR repeats
- (C)
PAM sequence
- (D)
sgRNA
GATE 2026 BT Q.26: solution and answer
Answer and solution
ANSWER
The component of the CRISPR/Cas9 system that is NOT of natural origin is (D) sgRNA.
Official answer: DSource: Official answer key, GATE 2026 BT (IIT Guwahati)
Recall the natural bacterial CRISPR-Cas9 adaptive immune system: it uses the Cas9 nuclease protein, arrays of CRISPR repeat-spacer sequences in the genome, and requires a PAM (protospacer adjacent motif) sequence on the target DNA next to the protospacer.
Option (A) CAS9 protein: naturally produced by bacteria such as Streptococcus pyogenes as part of their native immune defense system — of natural origin. Eliminate.
Option (B) CRISPR repeats: naturally occurring short repeated sequences interspersed with spacers in the bacterial genome, forming the memory of past phage infections — of natural origin. Eliminate.
Option (C) PAM sequence: a short motif naturally present in the target genomic DNA itself (of the invading phage/plasmid), required for native Cas9 to recognize and cleave the target — of natural origin. Eliminate.
Option (D) sgRNA (single guide RNA): in the natural bacterial system, Cas9 is guided by two separate RNA molecules — crRNA and tracrRNA — that base-pair with each other. The single-guide RNA used in genome-editing technology is a synthetic, laboratory-engineered fusion of these two natural RNAs into one chimeric molecule; this fused form does not exist in nature.
Therefore the component that is NOT of natural origin is sgRNA, option (D).
KEY IDEA
Natural CRISPR/Cas9 in bacteria uses Cas9 protein, a CRISPR repeat-spacer array, and PAM sequences on target DNA — all naturally occurring. The single-guide RNA (sgRNA) is a synthetic, laboratory-engineered fusion of the natural crRNA and tracrRNA into one chimeric molecule, created for genome-editing applications; it does not occur in this fused form in nature.
WATCH OUT FOR
Assuming any RNA involved in Cas9 targeting must be "natural" because RNA-guided cleavage itself is a natural bacterial process, and missing that the single-molecule sgRNA construct specifically is an engineered fusion (crRNA + tracrRNA) not found in native bacterial CRISPR systems.
From the GATE 2026 BT paper. Every question of this paper · Download the full paper · All 3 Editing & interactions questions, with notes