J. Craig Venter
J. Craig Venter and his colleagues have created a synthetic bacterial cell with 473 genes, the number they found are needed for self-replicating life. In doing so, the team has overturned a 20-year-old prediction about how many genes are essential--and revealed major gaps in our knowledge of the roles of these cornerstones of life.
The 473-gene synthetic bacterial cell is the result of a 20-year effort by Venter and his collaborators to build a cell from scratch. In 2010, a team at the J. Craig Venter Institute (JCVI) released version 1.0 of their synthetic cell. While the significance of the work was a topic of debate, JCVI presented it as evidence that it is possible to design genomes using computers. Since then, the team at JCVI and one of Venter's other organizations, Synthetic Genomics, have worked to refine the process, resulting in a synthetic bacterial cell that has significantly fewer genes than the earlier iteration.
JCVI-syn1.0, the 2010 synthetic cell, had 901 genes, 90% more than are found in the latest version. In cutting away nonessential genes, Venter's team think they have identified the bare bones needed for independent life. And, while the process has resulted in far fewer genes than were in JCVI-syn1.0, the number is bigger than many expected. Multiple studies have estimated just 200 to 300 genes are essential. "All the bioinformatics studies over the past 20 years have underestimated the number of essential genes," Venter said in a statement.
Venter attributes the discrepancy between the forecasts and the minimal synthetic bacterial cell to the tendency for bioinformatic predictions to focus "only on the known world." Of the 473 genes in JCVI's cell, the functions of 149 are unknown. When these genes, which are essential but for reasons that are currently unknown, are removed from the calculation, the number of genes in the synthetic cell are far closer to the predictions. The difficulty for the predictors was that even those running the synthetic cell project had little idea genes of unknown function were so prevalent.
"We expected that maybe 5% of the genes would be of unknown function. We weren't ready for 30%," Venter told The Atlantic. "We've discovered that we don't know a third of the basic knowledge of life. These are key biological functions affecting all of life that we don't understand."