Construction of a Bacterial Cell that Contains Only the Set of Essential Genes Necessary to Impart Life
Abstract
The primary goal of this research contract was to make a minimal bacterial cell as well as establish rules for grand scale based genome design. Our intent was to construct a new strain of the bacterium, Mycoplasma mycoides, controlled by a genome that contains only the essential genes necessary for growth in laboratory media with a doubling time of two hours or less. The project began with a conservative approach in which we would use information generated by gene disruption studies to make iterative, stepwise deletions. We would continue on to the next step only if the previous deletion mutant was viable and grew at a reasonable rate. While this steady approach would have ultimately proved successful, we followed a far faster and more efficient approach. The team developed a design, build, test system for generating a minimal cell. Briefly, minimized 1/8th genome segments were designed, tested in a 7/8th wild-type background and then combined into a minimized genome. Following multiple iterations of designs for the minimal genome, we have successfully created a strain controlled by a genome that is smaller than the genome of any other known organism capable of replication in pure culture. While we expect that there are approximately 34 additional genes that can be deleted, this represents a tremendous accomplishment. Perhaps more importantly, we have established a set of rules for genome minimization, and redesign that we believe can be applied to other bacteria to make them function for human purposes more efficiently and predictably.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 11, 2014
- Accession Number
- ADA613761
Entities
People
- Anthony Yee
- Clyde Hutchison
- Hamilton Smith
- John I Glass
Organizations
- J. Craig Venter Institute