March 10, 2017

expert reaction to five new artificial yeast chromosomes

Researchers publishing in Science have created five new synthetic yeast chromosomes with DNA from chemicals in a lab.

Dr Tom Ellis, Reader and Group Leader, Centre for Synthetic Biology and Department of Bioengineering, Imperial College London, said:

“Our collaborators in the consortium have shown that genome synthesis and recoding can work at the scale of millions of bases of DNA, covering more than a quarter of the entire yeast genome. Most importantly, they extensively demonstrate that the yeast cells containing these synthetic chromosomes are fit and healthy like normal yeast.

“Being able to make such huge changes throughout the genome is very exciting given the extensive use of yeast in modern biotechnology. Having synthetic chromosomes opens up a whole new route to improving production of chemicals, therapeutics and vaccines.

“These publications are a landmark moment for the world’s biggest synthetic biology project. It shows the scale and ambition of what can be achieved when researchers around the world work together.”

Prof Paul Freemont, Co-Director of the Centre for Synthetic Biology and Innovation, Imperial College London and Co-Director of SynbiCITE, Imperial College London, said:

“This work represents an amazing advance in our ability to chemically synthesise the blue print of life. Genomes are made up of DNA, a string or sequence of four different chemical building blocks abbreviated as A, T, G, C and it is these DNA sequences that encode the blue print (instructions) that power living organisms.

“This published work builds upon the pioneering work of Craig Venter and others who showed that a designed and chemically synthetic genome could be transplanted into simple bacterial cells replacing the natural genome and thus creating the first cell powered by a manmade genome. The Yeast synthetic genome project, which is a huge extension of this work, focuses on designing and synthesising the genome of Baker’s yeast, an ancient organism that humans have utilised for over 5,000 years to make bread, beer and wine and also more recently to manufacture drugs.  Yeast, surprisingly, is closely related to humans at the genetic level – to put this into context Baker’s yeast has 16 unique chromosomes (32 in total) and 12 million base pairs whereas humans have 23 unique chromosomes (46 in total) and 3 billion base pairs but despite these differences Baker’s yeast shares around 26% of its genes with humans. Therefore, studying the synthetic genome of yeast can help us to understand in part some of the complexity of the human genome.

“In terms of recent advances, I would suggest that the yeast synthetic genome project is potentially transformative. The ability to design, synthesise and assemble such complex chromosomes and get them to work in a living yeast cell is a massive achievement for synthetic biology. The fact that yeast cells with different synthetic chromosomes grow normally also shows that evolution has provided us with only one blueprint for life and through this work, and other work around recoding genomes, we are now beginning to realise that there may be many different genomic blueprints for life. The yeast project now allows us to explore these designs in a simple and well understood model cell.  Another major important aspect of the project in the context of a complex global landscape, is that it is international – teams of researchers from the US, China, Australia, Singapore and UK (Imperial and Edinburgh) are collaborating to construct and assemble a completely synthetic yeast genome clearly illustrating the international nature of scientific research.

“The project is moving rapidly to completion and it is likely that all the human-designed chromosomes will be fully synthesised by 2018. However, it is still unknown whether all the synthetic chromosomes will work together in a host yeast cell. If and when such a synthetic yeast cell is established it will tell us much about how genomes are organised, how they function and how they have evolved. The beauty of the designed chromosomes is that they also contain DNA signatures which allow easy rearrangements and swapping of DNA. BY allowing the chromosomes to scramble, we will be able to learn about genome function and evolution. Another important aspect of this is that we will also be able to develop new strains of Baker’s yeast which may be more amenable to industrial processes such as bread or beer making or manufacturing new drugs.

“From these and other recent advances, it is clear that the technology for genome synthesis is maturing to such an extent that researchers are looking for future genome synthesis projects which also includes the human genome. It is therefore essential that an open and transparent debate is initiated on the merits of future genome synthesis projects such that informed decisions can be made as to their benefits and risks.”

* ‘Building on nature’s design’ by Zahn et al. is one of a series of seven studies from the Synthetic Yeast Genome Project (Sc2.0) that published in Science on Thursday 9^th March.

Declared interests

Dr Ellis: ““I am a member of the Sc2.0 consortium.”

Prof. Freemont: “I am engaged with the Sc2.0 consortium via our Imperial efforts but am not leading any of the chromosome synthesis projects.”