Genomics of Actinobacteria: tracing the evolutionary history of an ancient phylum

Abstract

Actinobacteria constitute one of the largest phyla among bacteria and represent gram-positive bacteria with a high G+C content in their DNA. This bacterial group includes microorganisms exhibiting a wide spectrum of morphologies, from coccoid to fragmenting hyphal forms, as well as possessing highly variable physiological and metabolic properties. Furthermore, Actinobacteria members have adopted different lifestyles, and can be pathogens (e.g., Corynebacterium, Mycobacterium, Nocardia, Tropheryma, and Propionibacterium), soil inhabitants (Streptomyces), plant commensals (Leifsonia), or gastrointestinal commensals (Bifidobacterium). The divergence of Actinobacteria from other bacteria is ancient, making it impossible to identify the phylogenetically closest bacterial group to Actinobacteria. Genome sequence analysis has revolutionized every aspect of bacterial biology by enhancing the understanding of the genetics, physiology, and evolutionary development of bacteria. Various actinobacterial genomes have been sequenced, revealing a wide genomic heterogeneity probably as a reflection of their biodiversity. This review provides an account of the recent explosion of actinobacterial genomics data and an attempt to place this in a biological and evolutionary context.

FIG. 1.

Phylogenetic tree of Actinobacteria based on 1,500 nucleotides of 16S rRNA. Scale bar, 5 nucleotides. Families containing members subjected to complete genome sequencing at the time of this writing are depicted in bold. Orders are indicated.

FIG. 2.

Comparative genome maps of the prophage-like elements detected in Bifidobacterium genomes. Genes sharing similarity are linked. Probable functions of encoded proteins identified by bioinformatic analysis are indicated. The modular structure is color coded: red, lysogeny; green, DNA packaging and head; blue, tail; mauve, tail fiber; violet, lysis module; yellow, transcriptional regulator; orange, DNA replication; gray, unknown genes; black, genes similar to other functionally unknown bacteriophage genes. Vertical blue lines, tRNA genes.

FIG. 3.

Phylogenetic relationships of Rep proteins from actinobacterial plasmids and several prototype plasmids of different plasmid families from gram-positive and gram-negative bacteria. The phylogenetic tree was calculated by the sequence distance method using the neighbor-joining algorithm.

FIG. 4.

Circular map of genome diversity found in Tropheryma. From inside to outside: ring 1, GC deviation; ring 2, G+C content; ring 3, atlas of T. whipplei strain TW08/27; ring 4, comparison to the genome sequences of T. whipplei Twist. Green indicates homologies of >95%. The synteny plot comparing the order of homologous genes in sequenced genomes of Tropheryma is depicted in the panel inside the circular map.

FIG. 5.

(a) Genome map of Propionibacterium acnes KPA171202. The genome variability regions are indicated by black boxes. (b) Genome map of the P. acnes KPA171202 Pro-1 prophage. Probable functions of encoded proteins indicated by bioinformatics analysis are noted.

FIG. 6.

(a and b) Diagrammatic representation of the gene structures of the members of the PE and PPE gene family, displaying conserved 5′-end domains, motif positions, and differences between different subfamilies found in the two families modified by van Pittius et al. (446). (c) Alignment of the region surrounding the SVP motif Gly-XXSer-Val-Pro-XX-Trp in the members of the PPE-SVP subfamily. (d) Alignment of the region surrounding the GFGT motif (Gly-Phe-X-Gly-Thr) and the PPW motif (Pro-XX-Pro-XX-Trp) in the members of the PPE-PPW subfamily. (Modified from reference with permission from BioMed Central.)

FIG. 7.

Phylogeny of the M. tuberculosis complex, based on deleted regions as indicated by genomic analysis. Clustered along the vertical axis are organisms for which one or more genomic deletions specific for this evolutionary branch have been observed. The functions of the genes comprising the deleted regions are provided. (Modified from reference with permission.)

FIG. 8.

Synteny plot comparing the order of homologous genes (through their encoded proteins) in sequenced genomes of corynebacteria. The conservation between the C. jeikeium K411 genome and the genomes of C. glutamicum ATCC 13032, C. efficiens YS-314, and C. diphtheriae NCTC 13129 is shown by x-y plots of dots forming syntenic regions between the corynebacterial genomes. Each dot represents a CDS of C. jeikeium having a homolog in another genome, with coordinates corresponding to the CDS number in each genome. Homologs were identified by best BLASTP matches of amino acid sequences deduced from the 2,104 CDSs of C. jeikeium K411 with proteins encoded by C. glutamicum (3,002 CDSs; red dots), C. efficiens (2,950 CDSs; green), and C. diphtheriae (2,320 CDSs; blue).

FIG. 9.

Genetic organization of transposons localized in the genome of C. jeikeium K411. The detected transposons are arranged according to size. Predicted coding regions are shown as arrows. Different colors indicate transposase genes of ISs (blue), antibiotic resistance determinants (red), genes potentially involved in protective functions against environmental stress (orange), predicted transcriptional regulators (green), and genes involved in iron acquisition (magenta). Genes with other predicted functions are shown in yellow, and genes encoding hypothetical proteins are depicted in gray.

FIG. 10.

Loss of a large segment of duplicated DNA from S. coelicolor A3(2). Strain M145, used for genome sequencing, is a prototrophic, plasmid-free derivative obtained from the wild-type strain A3(2). After sequencing, it was discovered that A3(2) has much longer chromosomal TIRs than M145, and it was deduced that the reduction in length was probably because of homologous recombination between copies of ORF SCO0020. Black areas, conserved central unique region; hatched areas, region duplicated in A3(2) but not M145; white areas, extent of duplication in M145; dotted lines, genes omitted for clarity.

FIG. 11.

Inversions in the lineage of Streptomyces and Thermobifida fusca chromosomes. Dotted lines indicate the nonconserved ends of linear Streptomyces chromosomes (the T. fusca chromosome is circular). The origin of replication is indicated by a shaded oval. Connected arrows indicate inversion events deduced from overall synteny plots between chromosomes (65, 75, 194, 442). The diagram should be taken as an approximation of both the positions and frequencies of such events. There is only one clear example of a substantial inversion event that does not span the origin of replication (boldface arrows).

FIG. 12.

Sequential acquisition of developmental genes during the evolution of mycelial actinobacteria. The actinobacterial lineage, based on the occurrence of orthologs of S. coelicolor developmental genes, is shown in the shaded area. (Modified from reference with permission of the publisher.)

FIG. 13.

Relative intragenic positions of TTA codons in streptomycetes, Frankia, and T. fusca. Blue, S. coelicolor (Sco); pink, S. avermitilis (Sav); brown, S. scabies (Ssc); lilac, S. venezuelae (Sven); dark green, Frankia alni (Fal); light green, Frankia sp. strain Ccl3 (Fra); light brown, T. fusca (Tfu); red, E. coli (Eco); pale pink, M. tuberculosis (Mtb). TTA codons show a more pronounced bias in distribution towards the start of the gene in Streptomyces genomes.

FIG. 14.

Phylogenomic tree of the Actinobacteria phylum. The tree is based on the 123 protein sequences representing the minimal core gene sequences of Actinobacteria described in Table 7.

FIG. 15.

Taxonomic resolution of genomic approaches for assessing taxonomic relationships based on whole-genome sequences. These data are based on the results presented in the references cited in the text.

FIG. 16.

Diagram representing the distribution patterns of various Actinobacteria-specific proteins. The numbers of signature proteins are indicated.