In the latest study, Jef Boeke, a yeast biologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues tackled two chromosome segments that together represent about 1% of the 12-million-base-pair genome of the yeast Saccharomyces cerevisiae. The researchers designed the synthetic segments with the help of genome-editing software, incorporating several types of changes. These changes included removing repetitive sequences that could destabilize the genome, and adding tags to distinguish synthetic segments from natural ones. To create the genetic scrambling system, the team inserted short sequences that act as binding sites for a specific enzyme, which can delete or rearrange genes if activated. Overall, the researchers changed about 17% of the sequence in the targeted segments.
The edited segments were then synthesized and introduced into yeast cells, replacing the corresponding natural segments. Tests showed that the resultant semi-synthetic strains had apparently normal growth rates, colony appearance and gene expression. When the researchers turned on the scrambling system by activating the necessary enzyme, they were able to generate mutant strains with varying growth rates, drug sensitivity, temperature sensitivity, use of carbon sources and stress responses.