Synthetic yeast genome brings us closer to artificial life

Scientists have announced that they have successfully engineered from scratch a significant part of the DNA genome of yeast. The team have now made synthetic forms of 6 of yeast’s 16 chromosomes, which are the DNA hubs inside cells where genes are located. Inserted into yeast cells in place of the native chromosomes, these synthetic forms “booted up” and worked normally. This, researchers say, brings us closer to the goal of producing completely synthetic life. New York-based scientist Jef Boeke is leading the project, and he spoke to Chris Smith…

Jef - The papers that came out in Science this week describe the complete design of a synthetic version of the yeast genome, and that would be the yeast commonly used to brew beer and bake bread. It’s also a very important organism for basic science research and we’re announcing that five additional chromosomes have been synthesised to this design. They are alive and well inside a yeast cell and powering the normal growth of such a yeast cell.

Chris - Talk me through how you did that and for what reason?

Jef - We started with the genome spread out on a computer screen essentially. We wrote computer code to assist us in making systematic alterations to the genome sequence. To give you an example of how extensive that can be, something like one sixth of the bases or letters in the genome were either removed, altered, or replaced by a different sequence. So it’s really like a very heavily edited manuscript if you will. In fact, we sometimes jokingly refer to the computer code that we used to do this as “track changes for genomes,” if you’re familiar with the Microsoft word application.

After that is done the designed sequence is chopped up into very small bits of 100 DNA letters that can be synthesised on a machine, and there are many companies out there that make these small DNA’s referred to a oligonucleotides. Then these short snippets of DNA are strung together into ever larger pieces of DNA.

Then the final stage is that pieces of 60,000 DNA letters, or so, are mixed together with a yeast cell and they go and swap themselves into the chromosome, and remove the native material that’s there until the entire chromosome is replaced. The native DNA has gone and the synthetic DNA is there in its place.

Chris - So just to orientate people - when we’re talking about a chromosome, this is a molecule of DNA that has, potentially, thousands of genes in it, and those genes are made of individual letters of DNA. You have edited the DNA sequence in a computer, made an artificial form, assembled it, and then swapped in your assembled forms to replace those original DNA codes in the yeast chromosomes. So you end up, ultimately, with the yeast cell that have these artificial edited genomes working in them rather than their native original wild type genome.

Jef - I couldn’t have said it better myself.

Chris - But why - that’s the question? What’s the point of doing this and what does this prove, the fact that these cells can be booted up in this way and they’re running, they’re operating? What does that show us?

Jef - It shows us many things. One of the things that we’ve learned is that we can do remarkable things to the structure of those chromosomes. We can rearrange them in ways that haven't been seen in nature and the yeast seems to be not upset about these alterations and continues to grow very well despite the fact that we’ve moved huge chunks from one chromosome to another chromosome, for example.

Chris - Given the similarity between yeast cells and our own cells, would this in theory then, be possible to do with a human cell?

Jef - Yes, this would be possible, in principle, with any cell type from any organism. And some of my colleagues here in New York, and in other parts of the world, are very interested in engineering human cells to contain a synthetic genome, or synthetic chromosomes. We see many possible therapeutic benefits coming from this type of research. We could make systematic alterations to the genetic code in the human cells that would render those cells unable to be infected by a virus. This is based on work that was started in a colleague’s lab, George Church at Harvard.