Revolution in Biology: Semi-Synthetic Yeast Genome Opens New Horizons in Genetic Engineering
Revolution in Biology: Semi-Synthetic Yeast Genome Opens New Horizons in Genetic Engineering
Synthetic
DNA may seem like an idea from science fiction, but it is quickly becoming a
reality. In a breakthrough development, researchers have engineered a yeast
cell with a genome exceeding 50 percent synthetic content, featuring the
world's first fully synthetic chromosome.
Although
synthetic bacterial and viral genomes had been developed earlier, the
advancement of eukaryotic cells—whose genomes were enclosed within a
membrane-bound nucleus—represented a significant leap forward. The choice of
yeast, particularly baker's yeast (Saccharomyces cerevisiae), was strategic
because of its compact 16-chromosome genome and inherent DNA synthesis ability.
The
Synthetic Yeast Genome Project (Sc2.0) aims not only to synthesize DNA but also
to create a "designer" genome for yeast, which intends to depart
significantly from nature's blueprint. Senior author and Sc2.0 leader Jeff
Boeck emphasized the goal of building a yeast capable of uncovering new
biological insights.
The
creation of synthetic genomes involved the removal of "junk" DNA,
replaced by new DNA fragments that facilitate differentiation between
artificial and native genes. The gene order became random, and one important
change involved the extraction and transfer of t-RNA genes, which are notorious
for destabilizing yeast genomes. These tRNA genes were then transferred into a
breakthrough "neochromosome," marking the world's first fully de novo
synthetic chromosome.
The
researchers carefully combined each chromosome independently, resulting in 16
partially synthetic yeast strains, each containing 15 natural chromosomes and
one synthetic. The next challenge was to integrate all the synthetic
chromosomes into a single yeast cell, which was achieved through a combination
of classic genetic interbreeding and innovative methods such as chromosome
replacement and a CRISPR/Cas9-related technique.
Ultimately,
a single yeast cell harboring more than 50 percent synthetic DNA emerged,
exhibiting wild-type yeast-like survival and replication. This achievement
represents a rewrite of the operating system of budding yeast, ushering in a
new era of biological engineering—from tinkering with a few genes to designing
and constructing entire genomes.
Yeast,
an integral part of food and beverage production, as well as scientific
research, benefits significantly from synthetic DNA. Artificial chromosomes, as
a huge technological breakthrough, offer unprecedented opportunities in a
variety of fields, from environmentally friendly organic production to enhanced
understanding and combating of diseases.
When
the researchers reached their goal of incorporating all 16 synthetic
chromosomes into a single yeast cell, they considered the milestone "the
beginning of the end." This marks the beginning of a phase where
manipulating the yeast genome can lead to unprecedented efficiencies,
propelling biological engineering into
uncharted territory.
The journal cell contains the detailed description.
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