Researchers Build Synthetic Bacterial Cell With Just 473 Genes

Following the creation of the world’s first synthetic cell, Mycoplasma mycoides JCVI-syn1.0 in 2010, researchers at the J Craig Venter Institute and Synthetic Genomics have created the first minimal synthetic bacterial cell, JCVI-syn3.0. The cell, designed and constructed by scientists, has just 473 genes and 531,560 base pairs, making it the smallest genome of any organism that can be grown in laboratory media. The details of the project are published in the journal Science.

The cell’s minimal genome, at only 531 kb, contains the genes essential for life, along with a number of genes of unknown function. This makes it simpler than any autonomously replicating cell found in nature, and compares with the 1079-kb genome JCVI-syn1.0, which had 1.08 million base pairs and 901 genes, or the naturally-occurring Mycoplasma genitalium, which has 525 genes. The aim behind the cell’s creation is to create a cell so simple that the researchers will be able to understand the molecular and biological function of every single gene.

The researchers took the original synthetic cell, M mycoides JCVI-syn1.0, and used whole-genome design and synthesis techniques to minimise its genome. The initial design, which was based on a common set of 256 genes originally thought to be the minimum needed for viability, unfortunately failed to produce a viable cell. The researchers then identified a set of quasi-essential genes needed for robust growth that had not initially been included, which explained the failure of the first initial design. After three more cycles of design, synthesis, and testing, including building the genome in eight segments at a time to allow further testing, the team created JCVI-syn3.0, which was able to replicate, with a doubling time of around 180 minutes. The process also allowed the researchers to assign biological function to the majority of the genes with 41% of them responsible for genome expression information, 18% related to cell membrane structure and function, 17% related to cytosolic metabolism, and 7% preservation of genome information. The surprise was that 149 genes were still of unknown function, and the next step will be to understand the role of these genes in the cell.

What is interesting about this work is that it highlights both our lack of knowledge about biology – around one third of the genes have an unknown function. But does demonstrates how far the ability to engineer biology has progressed. It is also worth noting this isn’t yet a truly minimal bacteria as it still contains the quasi-essential genes. As it stands, the potential to carry a greater ‘genetic payload’ increasing the complexity of commercially useful protein product is intriguing and as it progresses further towards a truly minimal organism this is only likely to increase.