As part of a significant worldwide endeavor to create the first synthetic
yeast genome ever, a group of scientists located in the UK, under the
direction of specialists from the Universities of Nottingham and Imperial
College London, have finished building a synthetic chromosome.
The UK team's accomplishment, which is part of the largest synthetic
biology effort ever—the worldwide synthetic yeast genome
collaboration—represents completion of one of the yeast genome's sixteen
chromosomes. It was
published
in Cell Genomics.
Teams from the UK, US, China, Singapore, UK, France, and Australia have
been working together for 15 years on a project known as "Sc2.0" to create
synthetic replicas of every chromosome in yeast. In addition to this work,
nine more publications detailing the chromosomes that other teams have
created have also been published. It is anticipated that the genome project,
which is the biggest synthetic genome ever, would be completed in
2024.
The creation of a synthetic genome for a eukaryote—a living being with a
nucleus, including plants, animals, and fungi—has never been done before.
The chosen organism for the endeavor was yeast because of its comparatively
small genome and natural capacity to join DNA, which allowed the researchers
to create artificial chromosomes inside the yeast cells.
Yeast has a long history with humans; over thousands of years, we
domesticated it for baking and brewing, and more recently, we used it to
produce chemicals and as a model organism to understand how our own cells
function. Because of this link, yeast's genetics is more understood than
that of any other creature. Yeast was the apparent choice because of these
qualities.
The UK-based team, headed by Professor Tom Ellis of Imperial College London
and Dr. Ben Blount of the University of Nottingham, has recently stated that
their chromosome, synthetic chromosome XI, has been completed. The
chromosomal construction process took ten years, and the resulting DNA
sequence, which is made up of base pairs, or the "letters" that make up the
DNA code, is about 660,000 in length.
After a laborious debugging procedure, the synthetic chromosome that
substituted one of the natural chromosomes in a yeast cell allowed the cell
to thrive with the same fitness level as a natural cell. The synthetic
genome will have several uses in addition to assisting scientists in their
understanding of how genomes work.
The Sc2.0 synthetic genome has been constructed with additional traits that
provide cells unique skills not present in nature, rather than being a
direct clone of the natural genome. Thanks to one of these qualities,
scientists can make millions of distinct cell variants with varying
properties by forcing the cells to shuffle their gene content. Then,
individuals with better qualities can be chosen for a variety of uses in
biotechnology, bioenergy, and medicine. In essence, the procedure is
supercharged evolution.
Moreover, the group has demonstrated that their chromosome may be
repurposed as a novel tool for the investigation of extrachromosomal
circular DNAs, or eccDNAs. These are free-floating DNA circles that have
"looped out" of the genome and are being identified more and more as aging
factors, causes of malignant development, and a role in the resistance to
chemotherapy that many malignancies, including brain tumors from
glioblastoma, have to these drugs.
One of the project's principal scientists, Dr. Ben Blount, is an assistant
professor in the University of Nottingham's School of Life Sciences. "The
synthetic chromosomes are massive technical achievements in and of
themselves, but they will also unleash a plethora of new possibilities for
the study and application of biology," he declared. This can involve
developing novel microbial strains for more environmentally friendly
bioproduction or assisting in the research and treatment of illness."
"The synthetic yeast genome project is an amazing illustration of
large-scale science accomplished by a global consortium of researchers.
Being a part of such a massive endeavor where everyone engaged was working
toward the same common objective has been an amazing experience."
"By constructing a redesigned chromosome from telomere to telomere, and
showing it can replace a natural chromosome just fine," said Professor Tom
Ellis of the Imperial College London's Center for Synthetic Biology and
Department of Bioengineering, "our team's work establishes the foundations
for designing and making synthetic chromosomes and even genomes for complex
organisms like plants and animals."
The UK team comprises scientists from the universities of Edinburgh,
Cambridge, and Manchester in the UK, John Hopkins University and New York
University Langone Health in the U.S., and Universidad Nacional Autónoma de
México, Querétaro in Mexico, in addition to the leads from Nottingham and
Imperial College London.
Provided by
University of Nottingham
