How to Build a Minimal Cell?

What’s the smallest number of genes that cells need to grow and reproduce? Is it possible to synthesize minimal genomes and insert them into cells? What do minimal genomes teach us about life?

In this episode, we talk to John Glass, leader of the Synthetic Biology Group at the J. Craig Venter Institute. Over the past decade, Glass and colleagues developed techniques for manipulating and synthesizing entire bacterial genomes. Starting with Mycoplasma bacteria, which have very small genomes, they determined the minimal number of genes (473!) required to support life. They experimentally confirmed this number by synthesizing genomes from scratch, containing just the essential genes, and putting them into other bacteria whose genomes were removed. Cells in this lineage, called JCVI-syn3.0, grow and divide approximately like wildtype cells do.

We talk with John about how they pulled it off and what this minimal genome tells us about life more generally. We also chat about the functions of essential genes and what so-called non-essential genes may do in the wild. Finally, we touch on what if anything minimal genomes say about the origin of life and on the group’s ongoing efforts to synthesize entire cells – not just genomes! – from scratch.

Cover art by Keating Shahmehri