A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea

Abstract

Sequencing of bacterial and archaeal genomes has revolutionized our understanding of the many roles played by microorganisms. There are now nearly 1,000 completed bacterial and archaeal genomes available, most of which were chosen for sequencing on the basis of their physiology. As a result, the perspective provided by the currently available genomes is limited by a highly biased phylogenetic distribution. To explore the value added by choosing microbial genomes for sequencing on the basis of their evolutionary relationships, we have sequenced and analysed the genomes of 56 culturable species of Bacteria and Archaea selected to maximize phylogenetic coverage. Analysis of these genomes demonstrated pronounced benefits (compared to an equivalent set of genomes randomly selected from the existing database) in diverse areas including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of functions for known genes from other organisms. Our results strongly support the need for systematic 'phylogenomic' efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and Archaea' in order to derive maximum knowledge from existing microbial genome data as well as from genome sequences to come.

Figure 1

Maximum-likelihood phylogenetic tree of the bacterial domain based on a concatenated alignment of 31 broadly conserved protein-coding genes. Phyla are distinguished by colour of the branch and GEBA genomes are indicated in red in the outer circle of species names.

Figure 2. Rate of discovery of protein families as a function of phylogenetic breadth of genomes

For each of four groupings (species, different strains of Streptococcus agalactiae; family, Enterobacteriaceae; phylum, Actinobacteria; domain, GEBA bacteria), all proteins from that group were compared to each other to identify protein families. Then the total number of protein families was calculated as genomes were progressively sampled from the group (starting with one genome until all were sampled). This was done multiple times for each of the four groups using random starting seeds; the average and standard deviation were then plotted.

Figure 3. A bacterial homologue of actin

a, Genomic context of the bacterial actin-related protein (BARP) gene within the genome of the marine Delta proteobacterium H. ochraceum. Red, gene encoding BARP; white, genes encoding hypothetical proteins; black, genes with functional annotations. b, RT–PCR demonstration of expression of the gene encoding BARP in H. ochraceum. c, Ribbon plot of the putative structure of BARP. d, Alignment of BARP with actin from Dictyostelium discoideum with similarities in black shaded text. Secondary structure elements (arrows, beta-strands; bars, alpha-helices) are colour-coded as in c. A phylogenetic tree including this protein is in Supplementary Figure 1.

Figure 4. Phylogenetic diversity of bacteria and archaea on the basis of SSU rRNA genes

Using a phylogenetic tree of unique SSU rRNA gene sequences, phylogenetic diversity was measured for four subsets of this tree: organisms with sequenced genomes pre-GEBA (blue), the GEBA organisms (red), all cultured organisms (dark grey), and all available SSU rRNA genes (light grey). For each subtree, taxa were sorted by their contribution to the subtree phylogenetic diversity and the cumulative phylogenetic diversity was plotted from maximal (left) to the least (right). The inset magnifies the first 1,500 organisms. Comparison of the plots shows the phylogenetic ‘dark matter’ left to be sampled.