The natural starting point
The quest to define the simplest form of life often begins with Mycoplasma genitalium. First isolated in 1980 from two male patients in London, this bacterium has one of the smallest known genomes of any organism that can be grown in a lab. Its complete genetic sequence, published in 1995, revealed a single circular DNA molecule of 580,070 base pairs. This string of genetic code contains approximately 482 protein-coding genes.
M. genitalium is a human pathogen that can cause urogenital infections. Physically, it is one of the smallest self-replicating organisms, measuring just 0.2 to 0.7 micrometers. It has a distinctive flask-like shape and lacks a rigid cell wall, a characteristic of all bacteria in the class Mollicutes. This absence of a cell wall makes it resistant to common antibiotics like penicillin that target cell wall synthesis. Because its genome is so compact, with little redundancy, scientists identified it as a natural model for studying the essential genes required to sustain life.
Building life from scratch
Researchers at the J. Craig Venter Institute (JCVI) used M. genitalium as a blueprint for one of synthetic biology's most significant achievements: creating a cell with a minimal, synthetic genome. After creating the first synthetic cell in 2010 by synthesizing the larger genome of a related bacterium, the team set out to build a simpler version. Their goal was to determine the smallest set of genes necessary for an organism to live and replicate under laboratory conditions.
The result, announced in 2016, was a new, synthetic species named JCVI-syn3.0. This organism has a genome smaller than any found in nature for a self-replicating organism. It contains just 531,560 base pairs and 473 genes. The process involved designing the minimal genome on a computer, chemically synthesizing the DNA in fragments, and then assembling and "booting up" this new genetic software in a recipient cell. This minimal cell grows and divides, albeit more slowly than its natural counterparts. Remarkably, at the time of its creation, the biological function of 149 of its essential genes—nearly a third of the genome—remained unknown, showing how much is still to be learned about the basic mechanics of life.