Multiple origins of reverse transcriptases linked to CRISPR-Cas systems

Area of Science:

• Genomics and Molecular Biology
• Microbial Genetics
• Evolutionary Biology

Background:

• Prokaryotic genomes contain numerous uncharacterized reverse transcriptases (RTs).
• RTs related to group-II introns are found with type III CRISPR-Cas systems, potentially involved in RNA-mediated spacer acquisition.
• The evolutionary origins and domain relationships of these RTs are not well understood.

Purpose of the Study:

• To investigate the evolutionary origins and relationships of reverse transcriptases (RTs) associated with CRISPR-Cas systems.
• To identify the protein domains and phylogenetic lineages of these RTs.
• To provide new insights into the evolution of CRISPR-Cas/RT systems.

Main Methods:

• Conducted a large-scale survey of 198,760 annotated RT sequences from databases.
• Constructed a representative dataset of 9,141 unique RT sequences.
• Performed combined phylogenetic reconstruction and protein domain identification near CRISPR adaptation and effector modules.

Main Results:

• Identified three distinct evolutionary origins for CRISPR-associated RTs, indicating multiple independent emergence events.
• A major lineage evolved from group-II intron RTs; two minor lineages likely arose from Retron/retron-like sequences and Abi-P2 RTs.
• Discovered a novel group of RTs fused to archaeo-eukaryotic primase (AEP) domains within CRISPR-cas loci.

Conclusions:

• CRISPR-associated RTs have evolved independently multiple times from different ancestral sources.
• These RTs play a significant role in the evolution and diversity of CRISPR-Cas adaptive immunity.
• The findings offer a deeper understanding of the co-evolution of CRISPR-Cas systems and mobile genetic elements.