Progress continues on the Synthetic Yeast Project, an international scientific initiative that aims to build a yeast genome out of completely synthetic chromosomes.
The latest update involves seven papers published together in the journal Science detailing the five pre-designed chromosomes that have been successfully swapped into the genome of yeast. The model organism S. cerevisiae (Baker’s yeast) was chosen due to the detailed understanding of its genetic structure.
The researchers hope to be able to finish swapping in the rest of the organism’s 16 chromosomes by the end of the year, creating an entirely synthetic cellular life form.
Choosing A Model
When scientists were originally looking for a model organism to properly model eukaryotic cells decades ago, much like Escherichia coli is used as a model for prokaryotic ones, there were several factors to be considered.
The cells had to be large enough to make the viewing and modification of them simple, but they also had to grow and reproduce rapidly, while having a genome that wasn’t too overly complicated. And, of course, the monetary side of things demanded that the model chosen had to be easy to obtain for all scientists around the world.
Saccharomyces cerevisiae fit that bill perfectly. And its heavy usage since for industrial purposes across the board cemented its place as a useful model organism.
Now, back to the Synthetic Yeast Project. It should be pointed out that this is no simple construction of identical genomes manually and then inserting them. The swapped in chromosomes have been heavily modified. The ultimate eventual plan for the swapped in genome is for it to be 8% shorter than its original wild counterpart, with a total of 1.1 megabases of nucleotides either removed or altered.
The genome itself was created using an open-source design system called BioStudio, which allows for designing a eukaryotic genome and modeling alterations to nucleotides within it.
Then, the chromosomes were assembled individually by separate teams on the Project around the world, before slowly being brought together for the final assembling. While only a part of the genome has been swapped thus far, the overall process remains the same.
The method being used is referred to as “endoreduplication intercross”. Certainly a mouthful. Let’s start with the first half. Endoreduplication is a process found occasionally in the wild where the mitosis cycle of splitting a cell into two daughter cells is halted just before cytokinesis, the actual splitting.
What this results in is a complete cell with split and duplicated chromosomes. In a normal case, this would be an example of forced or purposeful polyploidy on the part of the organism, increasing its number of copies of its own genome.
But, as you could guess, this process by itself isn’t useful for the scientists, but it is necessary for the final construction. You see, while all the individual chromosomes are being made by teams around the world, they aren’t making them out in the open in thin air. They have to be made in yeast cells directly.
This means that we now have over a baker’s dozen of cells, each with a single desired synthetic chromosome in them. By inducing endoreduplication, the entire genomes are copied and are able to be “intercrossed” into other cells. This has to be done one at a time.
So, one of the yeast is crossed with another, resulting in a subsequent generation of yeast with two of the synthetic chromosomes. Do this with yet another and you have a generation with three. So on and so forth, up to the five thus far completed.
The entire process has to be done slowly to allow testing on the stability of the resulting genomes. Some further modifications have had to be made since to correct some parts of the chromosomes that were causing instability in the health of the yeast cell.
But, thus far, there have been no major perturbations of the consolidated cells. And, with the eventual fully synthetic genomes, scientists will be able to mass-copy them and then use them for extensive modification and testing on how chromosome structure works and how to replicate evolutionary processes.
The Work Continues
In short, due to the synthetic genomes being chemically generated, they are able to be fully customized after formation in any way desired, allowing a wide variety of scientific and possibly even medical research to take place.
Though all of that remains in the future at this point. With luck, the rest of the synthesis and integration of the chromosomes will be successfully completed by the end of the year with no problems or issues.
And then the real scientific work can begin.
Photo CCs: Yeast membrane proteins from Wikimedia Commons