Bacteria as computers making computers

Abstract

Various efforts to integrate biological knowledge into networks of interactions have produced a lively microbial systems biology. Putting molecular biology and computer sciences in perspective, we review another trend in systems biology, in which recursivity and information replace the usual concepts of differential equations, feedback and feedforward loops and the like. Noting that the processes of gene expression separate the genome from the cell machinery, we analyse the role of the separation between machine and program in computers. However, computers do not make computers. For cells to make cells requires a specific organization of the genetic program, which we investigate using available knowledge. Microbial genomes are organized into a paleome (the name emphasizes the role of the corresponding functions from the time of the origin of life), comprising a constructor and a replicator, and a cenome (emphasizing community-relevant genes), made up of genes that permit life in a particular context. The cell duplication process supposes rejuvenation of the machine and replication of the program. The paleome also possesses genes that enable information to accumulate in a ratchet-like process down the generations. The systems biology must include the dynamics of information creation in its future developments.

Fig. 1

A Turing machine involves physical separation between a machine and the program it expresses.

Fig. 2

The paleome and the cenome [adapted from Supplementary Figure 1, p. 76 Fang et al. Proteomics (2007) 7: 875–889]. Grouping genes according to their frequency in bacterial genomes (groups of 50 genes), with increased rareness (common genes on the left and rare genes on the right) reveals that both frequent genes and rare genes tend to remain clustered together in genomes (the horizontal lines gives the limit for statistical significance of grouping). Four hundred to 500 frequent genes (persistent genes) tend to stay clustered together despite the frequent shuffling and horizontal gene transfer in genomes.

Fig. 3

The tree of the distribution of genes in the mur-fts clusters does not follow 16S rRNA gene phylogeny, but is consistent with a tree based on the bacterial shape (modified from Tamames et al., 2001). On the left of the figure the mur-fts clusters are represented for different organisms. Black bars indicate genes located apart in the genome. Empty ovals represent intervening genes. The name of each species is coloured according to the shape of the cell; blue, bacilli; dark blue, Actinomycetes; green, cocci; orange, helicoïdal Deltaproteobacteria; red, Spirochetes.