Intraspecies comparison of Streptomyces pratensis genomes reveals high levels of recombination and gene conservation between strains of disparate geographic origin

Abstract

BackgroundStreptomyces are widespread bacteria that contribute to the terrestrial carbon cycle and produce the majority of clinically useful antibiotics. While interspecific genomic diversity has been investigated among Streptomyces, information is lacking on intraspecific genomic diversity. Streptomyces pratensis has high rates of homologous recombination but the impact of such gene exchange on genome evolution and the evolution of natural product gene clusters remains uncharacterized.ResultsWe report draft genome sequences of four S. pratensis strains and compare to the complete genome of Streptomyces flavogriseus IAF-45-CD (=ATCC 33331), a strain recently reclassified to S. pratensis. Despite disparate geographic origins, the genomes are highly similar with 85.9% of genes present in the core genome and conservation of all natural product gene clusters. Natural products include a novel combination of carbapenem and beta-lactamase inhibitor gene clusters. While high intraspecies recombination rates abolish the phylogenetic signal across the genome, intraspecies recombination is suppressed in two genomic regions. The first region is centered on an insertion/deletion polymorphism and the second on a hybrid NRPS-PKS gene. Finally, two gene families accounted for over 25% of the divergent genes in the core genome. The first includes homologs of bldB (required for spore development and antibiotic production) while the second includes homologs of an uncharacterized protein with a helix-turn-helix motif (hpb). Genes from these families co-occur with fifteen pairs spread across the genome. These genes have evidence for co-evolution of co-localized pairs, supporting previous assertions that these genes may function akin to a toxin-antitoxin system.ConclusionsS. pratensis genomes are highly similar with exceptional levels of recombination which erase phylogenetic signal among strains of the species. This species has a large core genome and variable terminal regions that are smaller than those found in interspecies comparisons. There is no geographic differentiation between these strains, but there is evidence for local linkage disequilibrium affecting two genomic regions. We have also shown further observational evidence that the DUF397-HTH (bldB and hpb) are a novel toxin-antitoxin pair.

Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

“…This analysis makes it possible to infer a gene's involvement in a GCF based on conservation over evolutionary time (34). Gene conservation within a GCF relies on the inclusion of multiple species in the analysis, as genome diversity within a single Streptomyces species is much reduced and synteny extends nearly the entire length of the chromosome (35). The tree shows distinct phylogenetic distributions of enzymes from different classes, as LanC and the C-terminal domains of LanM, LanL, and LanKC fall into four different clades (Fig.…”

Latitude delineates patterns of biogeography in terrestrial Streptomyces

“…There is also evidence for dispersal limitation at very large (continental) spatial scales with endemic species observed in North America and Central Asia (Wawrik et al ., ). Remarkably, genetic analysis of Streptomyces pratensis has revealed that strains of this species are in linkage equilibrium (i.e., random association of alleles at different loci) across a range that spans 1000 km (Doroghazi and Buckley, ). One interpretation of this finding is that Streptomyces are subject to widespread dispersal and unlimited gene flow at regional spatial scales.…”

Contributions of ancestral inter-species recombination to the genetic diversity of extant Streptomyces lineages

“…High rates of gene exchange between closely related strains may act as a cohesive force that reinforces the genetic similarity of species and species clusters (Doroghazi and Buckley, 2011). For example, strains of Streptomyces pratensis are in linkage equilibrium over much of their genome despite having a geographic range that spans 41000 km (Doroghazi and Buckley, 2014). This pattern of ancestry can result only if the S. pratensis genomes are recombining freely across a large geographic range, or if S. pratensis has experienced evolutionarily recent demographic expansion from an ancestral population that was in linkage equilibrium.…”