Genome plasticity and systems evolution in Streptomyces

Abstract

Background: Streptomycetes are filamentous soil-dwelling bacteria. They are best known as the producers of a great variety of natural products such as antibiotics, antifungals, antiparasitics, and anticancer agents and the decomposers of organic substances for carbon recycling. They are also model organisms for the studies of gene regulatory networks, morphological differentiation, and stress response. The availability of sets of genomes from closely related Streptomyces strains makes it possible to assess the mechanisms underlying genome plasticity and systems adaptation.

Results: We present the results of a comprehensive analysis of the genomes of five Streptomyces species with distinct phenotypes. These streptomycetes have a pan-genome comprised of 17,362 orthologous families which includes 3,096 components in the core genome, 5,066 components in the dispensable genome, and 9,200 components that are uniquely present in only one species. The core genome makes up about 33%-45% of each genome repertoire. It contains important genes for Streptomyces biology including those involved in gene regulation, secretion, secondary metabolism and morphological differentiation. Abundant duplicate genes have been identified, with 4%-11% of the whole genomes composed of lineage-specific expansions (LSEs), suggesting that frequent gene duplication or lateral gene transfer events play a role in shaping the genome diversification within this genus. Two patterns of expansion, single gene expansion and chromosome block expansion are observed, representing different scales of duplication.

Conclusions: Our results provide a catalog of genome components and their potential functional roles in gene regulatory networks and metabolic networks. The core genome components reveal the minimum requirement for streptomycetes to sustain a successful lifecycle in the soil environment, reflecting the effects of both genome evolution and environmental stress acting upon the expressed phenotypes. A better understanding of the LSE gene families will, on the other hand, bring a wealth of new insights into the mechanisms underlying strain-specific phenotypes, such as the production of novel antibiotics, pathogenesis, and adaptive response to environmental challenges.

Figure 1

The orthologous clusters identified by OrthoMCL. The parameters include the BLASTP cutoff E-values (10, 1, 0.1, 0.01, 10^-3, 10^-4, 10^-5, 10^-6, 10^-7, 10^-8, 10^-9, and 10^-10) and the MCL Markov clustering inflation indexes (1.0, 1.5, and 2.0).

Figure 2

The pan-genome of five Streptomyces species.

Figure 3

A schematic diagram showing the 5-hydroxyectoine biosynthesis gene cluster (strep3082-3085) that is conserved in the five Streptomyces genomes. The chromosome location of this cluster in each respective genome is: SCO1857-1873 for S. coelicolor, SAV_6407-6388 for S. avermitilis, SBI_08140-08124 for S. bingchenggensis, SGR_5639-5623 for S. griseus, SCAB_70821-70641 for S. scabiei. Blue: strep3082 (ectA), L-2,4-diaminobutyric acid acetyltransferase; magenta: strep3083 (ectB), L-2,4-diaminobutyrate aminotransferase; green: strep3084 (ectC), ectoine synthase; orange: strep3085 (ectD), ectoine hydroxylase; black: core genome components; gray: dispensable genome components; white: species-specific genes.

Figure 4

The distribution of gene families with lineage-specific expansions in five Streptomyces species. A. Distribution of the size of LSE gene families. B. Distribution of the size of lineage-unique LSE gene families. C. Distribution of the size of typical LSE gene families.

Figure 5

Graphic representation of a large gene block that has been duplicated in S. scabiei, drawn with the Mauve program [85]. The upper and middle panels depict the two respective duplicated clusters in S. scabiei. (SCAB_21721-22561 and SCAB_32241-33211). Only a single copy of this cluster is present in S. coelicolor (SCO6924-6843 (lower). Average sequence similarities are described as the height of the bars in each LCB (locally collinear block).

Figure 6

A phylogenetic tree of the two predicted lineage-unique ABC transporter families and antibiotic related ABC transporters from Streptomyces. The ABC transporters are divided into three classes. Type I: DrrA, S. peucetius; MtrA, S. argillaceus; KasK, S. kasugaensis; TnrB2, S. longisporoflavus; Type II: LmrC, S. lincolnensis; VarM, S. virginiae; OleB, S. antibioticus; SrmB, S. ambofaciens; CarA, S. thermotolerans; TlrC, S. fradiae; Type III: NovA, S. sphaeroides; NysG, NysH, S. noursei; StrW, StrV, S. glaucescens. The lineage-unique families are highlighted in green. The ABC transporters with proved antibiotic resistance function are highlighted in blue, and those not yet tested are highlighted in grey. Tree was inferred by the neighbor-joining method based on the amino acid sequences with Poisson corrected distance. The option of complete deletion of gaps was used for tree construction. 1,000 bootstrap replicates were used to infer the reliability of branching points. Bootstrap values of > 50% are presented. The scale bar indicates the number of amino acid substitutions per site. The Maximum Likelihood and Maximum Parsimony methods give virtually the same topology (data not shown).