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By exploring the evolutionary origin of an enzyme used in the CRISPR genome editing system, the researchers discovered more than 1 million other potential editors lurking in the microbial genome
.
The research, published in the September 9th issue of "Science", discovered a new editing enzyme in a protein family called IscB
.
These proteins are thought to be the ancestors of the Cas9 enzyme, which is called the molecular scissors of CRISPR
Ultra-precise CRISPR tools enhanced by enzyme engineering
Zhang Feng, the lead author of the study and a molecular biologist at the Massachusetts Institute of Technology in Cambridge, said that the discovery of other RNA-targeting enzymes that can cut DNA may provide further tools for genome editing
.
"These programmable proteins are very useful and go beyond basic biological interest," he said
Although researchers have used it for genetic engineering, CRISPR is 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
.
Computer studies have shown that Cas9 may have evolved from proteins in the IscB family, which are encoded by transposons or "jumping genes" that can jump to new positions in the genome
Zhang and his colleagues discovered that the DNA responsible for encoding the IscB protein is usually located near the DNA of a class of RNA molecules, which they call ωRNA
.
They also found that some IscB proteins can cut DNA at positions specified by the ωRNA sequence, just like Cas9 and its guide RNA
The team continues to study another protein family called TnpB, which is considered to be the ancestor of another dna slice Crispr-related enzyme called Cas12
.
They found that some of these proteins can also cut DNA under the guidance of ωRNA
Unexpected diversity
Soumya Kannan, a molecular biologist at the Massachusetts Institute of Technology (MIT) and one of the first authors of the study, said that the database search results showed that there are more than 1 million genes that may carry the code for the TnpB protein, and some organisms contain 100% of these genes.
Multiple copies
.
The IscB gene is not only found in bacteria and archaea, but also in light-absorbing chloroplasts in algae cells
.
This is the first time that such a genome editing system has been found in eukaryotes (an organism with a nucleus in the cell, including all plants and animals)-this surprising result shows that eukaryotes are more widespread than previously thought
In nature, these genes can perform various functions, including defense or regulating the expression of other genes
.
In the laboratory, this discovery may result in a large number of editing tools
For Gaetan Burgio, a geneticist at the Australian National University in Canberra, the real beauty of this research lies in its contribution to understanding evolution and, ultimately, its possible function for such a large and universal protein group as iscb
.
"It's absolutely fascinating," he said
.
"It fills an important gap: We really don't know how these CRISPR systems became CRISPR
.
"
