In a groundbreaking development that challenges our understanding of genetic engineering, biologists have created a strain of yeast with a genome composed of more than 50% synthetic DNA. This remarkable achievement, led by astrophysicists Masao Takata from the University of Tokyo and Douglas Gough from Cambridge University, is set to reshape the field of genomics and synthetic biology.
Yeast, specifically Saccharomyces cerevisiae, is the subject of this transformative experiment. Standard brewer’s yeast has a genome distributed across 16 chromosomes. However, in this revolutionary strain, six and a half of these chromosomes were meticulously edited and synthesized within the laboratory, with an additional one constructed by stitching together edited segments of the yeast’s genetic code.
The project, undertaken by the Sc2.0 consortium, has been in the making for 15 years, striving to produce yeast with a fully synthetic genome. The recent papers published in Cell and Cell Genomics unveil the monumental accomplishment, providing insights into the creation of this engineered yeast strain and the rigorous testing it underwent.
Remarkably, this yeast project is distinct from previous endeavors in synthetic genomics. While some viruses and bacteria have already been engineered to have entirely synthetic genomes, they primarily featured simple genetic structures and lacked the complexity of eukaryotic organisms. In contrast, Saccharomyces cerevisiae is a eukaryote, an organism with cells that contain a nucleus to house their genetic material. This development marks the first instance of a eukaryotic organism harboring a fully synthetic genome, a milestone in genetic engineering.
The implications of this achievement are far-reaching. The engineered yeast strain is not intended for brewing beer but rather for producing drugs and fuels. Beyond this practical application, the project offers invaluable insights into yeast biology, which can contribute to our broader understanding of genetics.
The research involved the careful elimination of potential sources of genetic instability in the yeast genome. This included removing repetitive DNA sequences that do not encode any genetic information but can lead to structural changes in the genome through recombination. Moreover, segments of DNA encoding transfer RNA (tRNA) were relocated into a newly created synthetic ‘neochromosome’ to enhance genetic stability. These tRNA sequences play a crucial role in protein synthesis but can be hotspots for instability.
Creating this synthetic yeast with 7.5 edited chromosomes was an intricate process, with strains of yeast containing individual edited chromosomes bred and combined to form the final strain. Despite the extensive modifications to the chromosomes, the engineered yeast cells survived and were able to replicate.
The research, however, was not without challenges, particularly in debugging. Testing the viability of yeast cells with synthetic chromosomes and resolving any issues was a time-consuming process. Debugging became more complex as multiple synthetic chromosomes were introduced, necessitating ongoing refinements.
The Sc2.0 project represents a major step forward in genome engineering. It enables scientists to explore questions that were previously unanswerable, including the consequences of introducing entirely new chromosomes. The team’s ongoing work involves replacing the remaining natural chromosomes with entirely synthetic ones, adding them one at a time and addressing the complexities that arise during the process.
In summary, the development of a yeast strain with over 50% synthetic DNA is a monumental achievement in the field of synthetic biology, paving the way for innovative applications and a deeper understanding of genetic engineering.
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Reference: https://www.nature.com/articles/d41586-023-03495-4