Science & Technology, UK (Commonwealth Union) – A team of scientists based in the UK, led by experts from the University of Nottingham and Imperial College London, has successfully constructed a synthetic chromosome as a pivotal milestone in a groundbreaking international initiative aimed at developing the world’s inaugural synthetic yeast genome.
Published recently in Cell Genomics, this achievement marks the finalization of one of the 16 chromosomes constituting the yeast genome by the UK team, a vital segment of the unprecedented synthetic biology project known as the international synthetic yeast genome collaboration, or ‘Sc2.0.’ This 15-year collaboration has engaged researchers from various countries, including the UK, US, China, Singapore, France, and Australia, all working collectively to create synthetic counterparts for all the chromosomes of yeast. Simultaneously with this publication, nine additional releases from different teams detailing their synthetic chromosomes are made public. The ultimate completion of the genome project, anticipated next year, will yield the most extensive synthetic genome ever created.
This pioneering endeavor signifies the first instance of constructing a synthetic genome for a eukaryote—a living organism with a nucleus, encompassing animals, plants, and fungi. The choice of yeast as the focal organism arises from its compact genome and inherent ability to fuse DNA, facilitating the construction of synthetic chromosomes within yeast cells.
With a rich history of domestication for baking, brewing, and recent applications in chemical production, yeast is a well-understood organism genetically, making it an ideal candidate. The UK team, spearheaded by Dr. Ben Blount from the University of Nottingham and Professor Tom Ellis at Imperial College London, reports the successful completion of synthetic chromosome XI. The decade-long project involved constructing a DNA sequence comprising around 660,000 base pairs, representing the letters of the DNA code.
Replacing a natural chromosome within a yeast cell, the synthetic chromosome, after meticulous debugging, enables the cell to grow with the same fitness level as a natural cell. Beyond unraveling genome functionality, the synthetic genome is poised for diverse applications. Unlike a mere replica of the natural genome, the Sc2.0 synthetic genome incorporates novel features that confer unique abilities to cells not found in nature. Notably, one feature empowers researchers to induce gene content shuffling, generating millions of cell variations with distinct characteristics. This capability holds promise for advancements in medicine, bioenergy, and biotechnology—a form of accelerated evolution with far-reaching implications.
Additionally, the team has demonstrated the adaptability of its synthetic chromosome as a novel platform for investigating extrachromosomal circular DNAs (eccDNAs). These are autonomous DNA circles that have extricated themselves from the genome, gaining recognition for their involvement in aging and their role as contributors to malignant growth and resistance to chemotherapy in various cancers, including glioblastoma brain tumors.
Dr Ben Blount, one of the lead scientists for the project, who is an Assistant Professor in the School of Life Sciences in the University of Nottingham. says “The synthetic chromosomes are massive technical achievements in their own right, but will also open up a huge range of new abilities for how we study and apply biology. This could range from creating new microbial strains for greener bioproduction, through to helping us understand and combat disease.
Professor Tom Ellis of the Centre for Synthetic Biology and Department of Bioengineering at Imperial College London, added “By constructing a redesigned chromosome from telomere to telomere, and showing it can replace a natural chromosome just fine, our team’s work establishes the foundations for designing and making synthetic chromosomes and even genomes for complex organisms like plants and animals.”
In addition to the leaders from Nottingham and Imperial College London, the UK team comprises scientists from the universities of Edinburgh, Cambridge, and Manchester in the UK, along with researchers from John Hopkins University and New York University Langone Health in the USA, and Universidad Nacional Autónoma de México, Querétaro in Mexico.
