A systems biology tour de force for a near‐minimal bacterium

Ever since the 1930s, when a handful of physicists, chemists, and biologists banded together into the phage school led by Max Delbruck, there have been efforts to understand life at its simplest and most fundamental level. In the ensuing decades up to the present, we have achieved a complete understanding of the genetic and chemical structure of a number of viruses, and know in many cases the role of all of their genes. The same cannot be said for cells. The simplest cells are bacteria, but they generally contain thousands of genes. The desire to understand how cells work has long attracted biologists to work with simple, near-minimal cells because of the assumption that smaller organisms with fewer molecular parts will be less complex and easier to understand. Whole genome sequencing and decades of biochemical studies have shown that the simplest known cells that are capable of growth in laboratory media are the atypical bacteria called mycoplasmas. The interest in these tiny bacteria as model systems to study cellular function led to two of them, Mycoplasma genitalium and Mycoplasma pneumoniae, being among the first few bacteria of which the genomes were sequenced (Fraser et al, 1995; Himmelreich et al, 1996). As those genome sequences were published in the mid-1990s, molecular and systems biology techniques have advanced to the point that the DNA sequences can be leveraged to gain a much deeper understanding of the biology of these minimal cells. A trio of papers published in Science by seven research groups coordinated by Peer Bork, Anne-Claude Gavin, and Luis Serrano offer an unprecedentedly detailed analysis of the transcriptional regulation, proteome organization, and metabolic regulation of the minimal bacterium M. pneumoniae (Guell et al, 2009; Kuhner et al, 2009; Yus et al, 2009).