Synthetic DNA may sound like the stuff of science fiction, but it’s rapidly becoming a reality. Researchers have created a yeast cell whose genome is more than 50 percent synthetic, including the world’s first fully synthetic chromosome.
Scientists have previously created synthetic genomes for bacteria and viruses, but the next step was for eukaryotic cells, cells whose genomes are contained entirely within a membrane-enclosed nucleus. Perhaps yeast, as baker’s yeast, was naturally selected for this (budding yeast) have a compact genome of just 16 chromosomes and an innate ability to string DNA together.
But researchers behind the Synthetic Yeast Genome Project (Sc2.0) wanted to do something a little different than just DNA synthesis by giving yeast a “designer” genome. “We decided it was important to create something significantly modified from nature’s design,” said senior author and his Sc2.0 leader Jeff Bork. states. statement. “Our main goal was to build a yeast that could teach us new biology.”
Creating a synthetic genome
The researchers first removed so-called “junk” DNA from the genome and replaced it with new DNA fragments so they could distinguish between synthetic and natural genes. We then shuffled the order of the genes. Another important deletion was also made: the tRNA gene.
Although the proteins encoded by tRNA genes play important roles within cells, tRNA genes also destabilize the yeast genome. In a revolutionary step, the researchers removed them and replaced them with an entirely new, entirely t-RNA gene-based “neochromosome.” “The tRNA neochromosome is the world’s first completely de novo synthetic chromosome,” said co-author Patrick Yizhi Cai. “Nothing like this exists in nature.”
In addition to the neochromosome, the researchers created 16 partially synthetic yeast strains, each with 15 natural chromosomes and one synthetic chromosome, after assembling each chromosome independently.
combine the pieces
Next came the difficult part of getting all the synthetic chromosomes into a single yeast cell. This required a combination of classic genetic techniques, crossbreeding, and some new techniques. Cross-breeding was slow and the resulting yeast genome was more than 30% synthetic, but researchers wanted more.
After repairing the genetic defect using a new method called chromosome replacement and a CRISPR/Cas9-like technology, they achieved a single yeast cell with more than 50 percent synthetic DNA. Tinkering with the genome could have caused the yeast to grow or look abnormal, but careful engineering allowed it to survive and even reproduce like wild yeast. .
“The team has now rewritten the operating system of Saccharomyces cerevisiae. This opens a new era in engineering biology, moving from modifying a few genes to de novo designing and building entire genomes. ” said Kai.
next step
Yeast has long been essential in the production of both food and drinks. It’s why we have decent bread and beer and why everyone says, “Thank you, yeast.” They have also been used in the field of science to produce chemicals and as model organisms. As one of the leading scientists, Ben Brandt, explains, synthetic DNA allows us to make some advances in these areas. statement.
“Synthetic chromosomes are a major technological achievement in themselves, but they also open up a wide range of new capabilities in how we study and apply biology. This could range from creating strains to helping to understand and fight diseases.
The next step is to incorporate all 16 synthetic chromosomes into a single yeast cell. This is no mean feat, but researchers are hopeful. “Right now, we’re still so far from the finish line that he has all 16 chromosomes in one cell,” Boeke said.
“I like to call this the end of the beginning, not the beginning of the end, because that’s when we really start shuffling the deck and doing things we’ve never seen before. Because we can start producing yeast that can do this.”
The research will be published in a journal cell.