Scientists Discover 188 New Rare CRISPR Genes, Including Novel Type VII System

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Using New Algorithm, Researchers Uncover Rare and Unknown CRISPR-Cas Systems

Researchers have made a groundbreaking discovery utilizing a new algorithm called FLSHclust (flash clust) that has revealed 188 rare and previously unidentified CRISPR-linked gene modules. These gene modules include an entirely novel type VII CRISPR-Cas system. The algorithm’s findings provide an extraordinary opportunity to harness CRISPR systems and gain a deeper understanding of the vast functional diversity of microbial proteins.

The CRISPR-Cas systems have revolutionized biotechnology and have been instrumental in the development of various biomolecular approaches. These approaches include the highly acclaimed CRISPR/Cas-mediated genome editing technique. The recent discovery of previously unknown CRISPR systems has the potential to propel the research and development of these biotechnologies even further, leading to the creation of safer and more effective genomic therapeutics.

In recent years, computational searches of protein sequence databases have expanded the CRISPR toolbox. However, the existing algorithmic approaches have proven impractical when it comes to analyzing exponentially growing datasets containing billions of proteins. Addressing this limitation, Han Altae-Tran and their team have developed a game-changing algorithm called FLSHclust (fast locality-sensitive hashing-based clustering). This algorithm enables the rapid and efficient analysis of vast protein sequence databases, unlike any other method currently available.

To evaluate the effectiveness of their approach, Altae-Tran et al. employed FLSHclust to conduct a search for rare CRISPR systems. They targeted an 8.8 terrabase pair metagenomic database, housing a staggering 8 billion proteins and 10.2 million CRISPR arrays. Through this analysis, the team unveiled 188 previously undiscovered CRISPR-associated genes. Additionally, they identified and meticulously characterized an entirely new class of Cas-14 containing CRISPR system, referred to as type VII, which predominantly acts on RNA.

Findings from this study indicate that the newly identified CRISPR systems are exceptionally rare. Many of them only form a single cluster out of the nearly 130,000 CRISPR-linked clusters revealed by FLSHclust. The authors of the study emphasize the significant expansion of known CRISPR diversity with the discovery of previously unknown cas genes and CRISPR systems. This expansion showcases the functional versatility of CRISPR, where new proteins and domains are often recruited, either replacing existing components or bestowing new functions upon the existing Cas protein scaffold.

In conclusion, this groundbreaking research not only demonstrates the unprecedented organizational and functional flexibility and modularity of CRISPR systems but also highlights that the majority of these variants are rare. They are found primarily in relatively unusual bacteria and archaea. The findings from this study open up new possibilities for advancing biotechnology through enhanced understanding and utilization of CRISPR systems.

Hundreds of rare and unidentified CRISPR-Cas systems have been discovered using a new algorithm known as FLSHclust (flash clust). The algorithm analyzed billions of protein sequences and uncovered 188 previously unknown CRISPR-linked gene modules, including a novel type VII CRISPR-Cas system. The discovery provides exciting opportunities for further harnessing CRISPR systems and exploring the immense functional diversity of microbial proteins. Researchers believe these findings could lead to safer and more effective genomic therapeutics and expand the CRISPR toolbox. The algorithm, FLSHclust, enables quick and efficient analysis of vast protein sequence databases. It was successfully used to search for rare CRISPR systems in an 8.8 terrabase metagenomic database, leading to the identification of 188 previously unknown CRISPR-associated genes. The researchers also characterized a new class of Cas-14 containing CRISPR system, type VII, that targets RNA. The study highlights the incredible versatility and modularity of CRISPR systems while underlining their rarity and association with unusual bacteria and archaea. The findings pave the way for further advancements in biotechnology and a deeper understanding of CRISPR systems.

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