Leap forward made in synthetic biology
3 Apr 2017 by Evoluted New Media
An international team of more than 200 researchers have made significant progress in building an organism from scratch.
An international team of more than 200 researchers have made significant progress in building an organism from scratch.
The consortium, known as Saccharomyces cerevisiae 2.0 (Sc2.0), have managed to synthesise five of the 16 chromosomes found in yeast. This means 30% of the yeast’s genetic material has been replaced with engineered replacements. Seven papers have been published in one issue of Science to highlight the work.
Professor Jeff Boeke, from New York University and Sc 2.0 project director, said: “This work sets the stage for completion of designer, synthetic genomes to address unmet needs in medicine and industry. Beyond any one application, the papers confirm that newly created systems and software can answer basic questions about the nature of genetic machinery by reprogramming chromosomes in living cells.”
In 2014, the first synthetic yeast chromosome – synthetic chromosome 3 or synIII – comprising 272,871 base pairs, was assembled by the researchers. The papers published in Science also describe the assembly of synII, synV, synVI, synX and synXII. Many technologies developed for Sc2.0 form the basis for GP-write, an initiative aiming to synthesise complete sets of human and plant genomes in the next decade.
The researchers are aiming to design and build synthetic versions of all 16 chromosomes for S. cerevisiae before 2018. Using computer programs, the researchers removed gene sequences found in natural yeast, without any negative effects. These included retrotransposons, TY1 elements and other multi copy genes thought dispensable.
Professor Boeke said: “You can design a genome from scratch on a computer and make extensive changes to the genome, based on prior knowledge, and get out very healthy yeast. You can use this to make lots of new discoveries by employing its ‘scrambling’ system which normal yeast doesn’t have. The yeast genome is very plastic.”
The scrambling system introduced into the synthetic yeast mimics random variation that can lead to evolution. When activated, it randomly duplicates, shuffles and deletes genes – and will potentially allow future studies to explore evolutionary changes as well as introduce more radical changes into synthetically produced yeast.
The individual articles are listed below: 1. Design of a synthetic yeast genome 2. Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome 3. “Perfect” designer chromosome V and behaviour of a ring derivative 4. Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond 5. Bug mapping and fitness testing of chemically synthesised chromosome X 6. Engineering the ribosomal DNA in a megabase synthetic chromosome 7. 3D organisation of synthetic and scrambled chromosomes
