Humans have some 20,000 genes. The most well-studied microbe, E. coli, has some 4,000 genes. And the record for a free-living species is held by Mycoplasma genitalium, with 525 genes.
Now, the pioneering scientist Craig Venter and his colleagues have engineered a bacterium to have only 473 genes. “It is a profound result,” Adam Arkin of Berkeley Synthetic Biology Institute told Quartz.
This is a huge leap toward the ultimate goal of synthetic biology: designing life from scratch, where we know what each gene does. When we get there, it will open up infinite possibilities. In theory at least, we could eventually have bacteria making personalized medicines and algae producing biofuels.
To build Syn 3.0, Venter and his colleagues started with a bacterium they had designed in 2010, Syn 1.0, which had some 900 genes. They made Syn 1.0 by removing the naturally occurring genome of bacteria Mycoplasma mycoides and replacing it with a lightly tinkered version that they made in a lab. This was a unique achievement because Syn 1.0 lived with the synthetic genome.
For Syn 3.0, they began knocking out non-essential genes from Syn 1.0. Their first target was to remove genes that occurred in pairs. In many cases the cell kept working with only one copy of the gene. Next they started removing genes whose functions they didn’t know. But then they hit problems. Not knowing the function of a gene did not mean it was not essential for life.
What is “essential” for life depends on the environment that a living cell finds itself in. For instance, the record for the life-form with the fewest genes is held by naturally occurring Tremblaya, which has only 120 genes. But it cannot survive outside its insect host, which is performing many of the critical functions for Tremblaya. That is why Venter’s team wanted “essential” to mean what would be necessary for the organism to live on its own.
Without knowing what all those essential genes are, Venter and his colleagues took a trial-and-error approach. If one of their designed genomes created a living cell, then they would remove a specific gene from it and see if it still lived. If it didn’t, then they would restore that gene and remove another. After doing this for a few years, they got to Syn 2.0 with 516 genes. They kept going until they reached Syn 3.0, with 473 genes.
This is a historic step forward in human knowledge, to be sure, but there remains a certain amount that’s unknowable. Though Syn 3.0 is the free-living cell with the fewest number of genes, Venter and his colleagues still don’t know what 149 of those 473 genes do. If you asked an engineer to build a plane where she doesn’t know what a third of the parts do, she’ll say you are crazy.
So Venter and his colleagues are working on understanding and tinkering with those genes, and they’ve already made progress. They took some 60 genes of Syn 3.0 and reordered them according to their function. The resulting genome, like a defragmented hard drive, was leaner and worked just as well.
This kind of tinkering is of huge significance for synthetic biologists. If they know what each gene does, the hope is that they’ll design life that may be able to do something that, until now, no species can do.