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Bacteriophages (seen here attacking bacterial cells) may use the CRISPR-Cas system to compete with each other — or manipulate gene activity
in the host.
Systematic scanning of viral genomes revealed a plethora of potential CRISPR-based genome editing tools
.
The CRISPR-Cas system is common in the microbial world of bacteria and archaea that normally help cells fight off viruses
.
But an analysis published Nov.
23 in the journal Cell found that the CRISPR-Cas system
is present in 0.
4 percent of the public genome sequences of viruses that can infect these microbes.
The researchers believe that these viruses use CRISPR-Cas to compete with each other and potentially manipulate the host's gene activity to their advantage
.
Some of these viral systems are capable of editing the genomes of plants and mammals and are characterized by their compact structure and high editing efficiency, which can make them useful
in the laboratory.
Kira Makarova, a computational biologist at the National Center for Biotechnology Information in Bethesda, Maryland, said: "This is an important step
forward in discovering the enormous diversity of the CRISPR-Cas system.
A lot of novelty
was found here.
”
Although CRISPR-Cas is best known as a tool used in the lab to alter genomes, it can function
in nature as a basic immune system.
About 40 percent of the sample bacteria and 85 percent of the sample archaea had the CRISPR-Cas system
.
Typically, these microbes can capture fragments of the genome of invading viruses and store the sequences in their own genomic regions, called CRISPR arrays
.
The CRISPR array then acts as a template to generate RNA, which guides CRISPR-associated (Cas) enzymes to cut the corresponding DNA
.
This could allow the microbes carrying the array to cut the viral genome and potentially stop viral infections
.
Viruses sometimes acquire fragments of the host genome, and researchers have previously found isolated examples
of CRISPR-Cas in viral genomes.
If these stolen pieces of DNA give the virus a competitive advantage, they can be preserved and gradually modified to better serve the virus's lifestyle
.
For example, a virus infected with Vibrio cholerae uses CRISPR-Cas to cut and disable the bacteria's DNA, which encodes antiviral defenses
.
Jennifer Doudna, a molecular biologist at the University of California, Berkeley, and Jillian Banfield, a microbiologist, and their colleagues decided to conduct a more comprehensive study
of the CRISPR-Cas system in viruses that infect bacteria and archaea (bacteriophages).
To their surprise, they found about 6,000 such genes, including representatives of
all known types of the CRISPR-Cas system.
"There is evidence that these systems are useful for bacteriophages," Doudna said
.
The team found widespread variation in the usual CRISPR-Cas structure, with some systems missing components and others unusually compact
.
Anne Chevallereau, who studies phage ecology and evolution at the French National Centre for Scientific Research in Paris, said: "Even though phage-encoded CRISPR-Cas systems are rare, they are highly diverse and widely distributed
.
Nature is full of surprises
.
”
The viral genome tends to be compact, and some viruses have very small
Cas enzymes.
This may provide a particular advantage for genome editing applications, as smaller enzymes are easier to shuttle into cells
.
Doudna and her colleagues focused on a group of small Cas enzymes called Casλ, some of which they found could be used to edit lab-grown genomes
from Arabidopsis thaliana (Arabidopsis), wheat, and human kidney cells.
The results show that viral Cas enzymes can join the growing number of gene-editing tools found in microbes
.
Doudna said that although researchers have discovered other small Cas enzymes in nature, many of them have so far been relatively inefficient
in genome editing applications.
In contrast, some viral Casλenzymes combine small volume and high efficiency
.
In the meantime, researchers will continue to look for potentially improved microbes
for known CRISPR-Cas systems.
Makarova expects that scientists will also look for CRISPR-Cas systems
that are captured by plasmids (fragments of DNA that can be transferred from microbes to microbes).
"Every year we have thousands of new genomes available, some of them from very different environments
," she said.
So it's really going to be fun
.
”
