This is the first time that scientists have attempted to create the genome of a eukaryotic organism from scratch, a huge milestone.
Humans have had a close relationship with yeast for thousands of years. It has been used for baking and brewing since time immemorial. More recently, yeast has also been used in chemical production and as a model organism to understand how our own cells function. Thanks to this long history and intensive study, we know the genetics of yeast better than those of any other organism. And researchers are now making good use of this. They have now succeeded in creating semi-synthetic yeast in the laboratory. And that is promising. Completely rewriting the yeast genome could lead to the creation of a new yeast variant that is stronger, grows faster, has a higher yield and is better able to withstand challenging conditions.
Chromosomes
Gist (Saccharomyces cerevisiae) consists of a total of 16 chromosomes. And an artificial version has now been created for each of these chromosomes, scientists write in two separate studies (which here in here can be read). “Our goal is to understand the basic principles of genomes by constructing synthetic genomes,” explains researcher Patrick Yizhi Cai. “We have now completely overhauled the operating system of baker’s yeast, heralding a new era in biotechnology. We are going from tinkering with just a few genes to fully designing and building entire genomes.”
One yeast cell
Because the yeast genome is divided into sixteen chromosomes, scientists started by building each chromosome separately. This resulted in sixteen partially synthetic yeast strains, each containing 15 natural chromosomes and one synthetic chromosome. The next challenge was to combine these synthetic chromosomes into one yeast cell. To achieve this, the researchers crossed several partially synthetic yeast strains and then looked among their offspring for individuals that carried both synthetic chromosomes. Ultimately, the team managed to gradually consolidate all previously synthesized chromosomes – seven in total – into a single yeast cell. The yeast strain they ultimately created consists of more than 50 percent synthetic DNA. This strain is able to survive and multiply in the same way as wild yeast strains.
Synthetic eukaryotic genome
The study is a great step forward. Because although scientists have synthesized bacterial and viral genomes before, this is the very first attempt to create an artificial genome of a eukaryotic organism – a living organism with a cell nucleus. “The global Yeast 2.0 project is trying to do something that has never been done before,” says researcher Tom Williams. “This is the first time we are trying to create the genome of a eukaryotic organism, which can also include humans.” Yeast was specifically chosen for this project because of its compact genome and ability to link DNA together, allowing scientists to build synthetic chromosomes in yeast cells.
Designergenoom
In short, with the study, the researchers have taken a major step towards a designer genome for baker’s yeast. This genome differs significantly from the natural genome of yeast used in breweries and bakeries. “We chose to create something that deviates significantly from the natural form,” says researcher Jef Boeke. “Our ultimate goal is to develop a yeast strain that can provide us with new insights into biology.”
Differences
The synthetic genome is therefore anything but an exact copy of the natural genome. And that’s on purpose. For example, the synthetic genome has new properties that give cells unique characteristics that you do not find in nature. One of these properties allows scientists to rearrange the genes of cells, allowing them to create millions of different versions of cells with different characteristics. They can then select the cells that are best for specific applications in medicine, bioenergy and biotechnology.
Milestone
The researchers are therefore very enthusiastic. “This is an exciting achievement in the field of biotechnology,” Cai underlines. “Although we have been able to edit genes for quite some time, writing a eukaryotic genome is something completely new from the very beginning. This work is crucial to our understanding of the fundamentals of life and has the potential to transform the world of synthetic biology.” The creation of the synthetic chromosomes is a major technical achievement in itself, but it will also enable new ways to study and use biology. This can range from creating new microbial strains for more environmentally friendly bioproduction to helping understand and combat diseases.
The ultimate goal of this project is to merge all individual synthetic chromosomes into a fully synthetic cell. The team aims for this man-made yeast to be as potent and healthy as wild yeast. This strain will not only be the very first synthetic eukaryote, but also the first to be co-created by scientists around the world. “We are now on the verge of combining all sixteen chromosomes in one cell,” says Boeke. “I consider this the completion of the beginning, not the beginning of the end. The real adventure only begins when we discover what fantastic things we can achieve with this yeast, things we cannot yet imagine.”
