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Who are the ancestors of the CRISPR enzyme? |
In the past decade, scientists have applied the CRISPR system to gene editing technology, a precise and programmable system for modifying DNA
.
Recently, researchers have explored the evolutionary origin of an enzyme used in this system and discovered a new programmable DNA modification system
"China Science News" learned from the Massachusetts Institute of Technology and the Broad Institute of Harvard University that the protein called OMEGA (obligate mobile element guided activity) discovered by the institution's molecular biologist Zhang Feng and others may be Naturally participate in the reorganization of small fragments of bacterial genome DNA
.
Related papers were recently published in "Science"
Researchers discovered OMEGA in a family of proteins called IscB
.
These proteins are considered to be the ancestors of the Cas9 enzyme.
"This RNA-guided DNA recognition mechanism is probably something that nature has independently created many times
.
" Zhang Feng said, "These results show that there are more effective programmable systems waiting to be discovered and developed
Programmable enzymes, especially those that use RNA guidance, can be quickly adapted to different uses
.
For example, CRISPR has always been considered a microbial defense system that allows bacteria and other single-celled organisms called archaea to "chew" the DNA of viruses and other genetic invaders by sending Cas9
This time, the researchers discovered that the DNA responsible for encoding IscB is usually located near the DNA of a type of RNA molecule called ωRNA
.
They also found that some IscBs can cut DNA at positions specified by the ωRNA sequence, just like Cas9 and its guide RNA
The team also studied another protein family called TnpB, which is thought to be the ancestor of the Cas12 enzyme
.
They found that some of these proteins can also cut DNA under the guidance of ωRNA
Soumya Kannan, the first author of the paper and a molecular biologist at the Massachusetts Institute of Technology, said that the database search results showed that there are more than 1 million genes that may carry the TnpB protein code, and some organisms contain more than 100 copies of these genes
.
In fact, the IscB gene is not only found in bacteria and archaea, but also in light-absorbing chloroplasts in algae cells
.
Therefore, this is the first time that researchers have discovered such a genome editing system in eukaryotes
In addition, the team found that IscB can be used to cut human DNA, although its efficiency is lower than that of the CRISPR-Cas9 system
.
But the IscB system can be improved, and the small size of the IscB may make it more suitable for certain applications
.
Australian National University geneticist Gaetan Burgio believes that this research has promoted people's understanding of the evolution of the CRISPR-Cas9 system and has given possible functions to such a universal protein family as IscB
.
He said, “It fills an important gap: We don’t know how these CRISPR systems become'gene shears'
.
” (Source: China Science News Tang Yichen)
Related paper information: https://doi.
org/10.
1126/science.
abj6856
org/10.
1126/science.
abj6856