They started with bacteria from the genus Mycoplasma; these cells have some of the smallest genomes ever sequenced. Thus, they are excellent tools for engineering synthetic genomes.
In their most recent publication, Venter and his team set out to “minimize the 1,079 kbp synthetic genome of M. mycoides JCVI-syn1.0”. They used transposon mutagenesis to determine which genes were essential and which could be done away with. Their work eventually produced JCVI-syn3.0, a cell whose genome is 531 kbp and that contains only 473 genes. “Its genome is smaller than that of any autonomously replicating cell found in nature”, say authors.
This approach seems simple enough, right? Not so. Many genes didn’t fall into clear-cut “essential” or “nonessential” categories. Instead, they found a number of “quasi-essential” genes that are required for robust growth (but not necessarily viability).
According to the study authors, “JCVI-syn3.0 is a working approximation of a minimal cellular genome, a compromise between small genome size and a workable growth rate for an experimental organism. It retains almost all the genes that are involved in the synthesis and processing of macromolecules. Unexpectedly, it also contains 149 genes with unknown biological functions, suggesting the presence of undiscovered functions that are essential for life.”
Sources: Science Daily, Science, Wikipedia