Abstract
BackgroundCompleted genome sequences are rapidly increasing for Rickettsia, obligate intracellular α-proteobacteria responsible for various human diseases, including epidemic typhus and Rocky Mountain spotted fever. In light of phylogeny, the establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout the rickettsial tree (class 2 OG or C2OGs).Methodology/Principal FindingsWe present 1823 representative (no gene duplications) and 259 non-representative (at least one gene duplication) rickettsial OGs. While the highly reductive (∼1.2 MB) Rickettsia genomes range in predicted ORFs from 872 to 1512, a core of 752 OGs was identified, depicting the essential Rickettsia genes. Unsurprisingly, this core lacks many metabolic genes, reflecting the dependence on host resources for growth and survival. Additionally, we bolster our recent reclassification of Rickettsia by identifying OGs that define the AG (ancestral group), TG (typhus group), TRG (transitional group), and SFG (spotted fever group) rickettsiae. OGs for insect-associated species, tick-associated species and species that harbor plasmids were also predicted. Through superimposition of all OGs over robust phylogeny estimation, we discern between C1OGs and C2OGs, the latter depicting genes either decaying from the conserved C1OGs or acquired laterally. Finally, scrutiny of non-representative OGs revealed high levels of split genes versus gene duplications, with both phenomena confounding gene orthology assignment. Interestingly, non-representative OGs, as well as OGs comprised of several gene families typically involved in microbial pathogenicity and/or the acquisition of virulence factors, fall predominantly within C2OG distributions.Conclusion/SignificanceCollectively, we determined the relative conservation and distribution of 14354 predicted ORFs from 10 rickettsial genomes across robust phylogeny estimation. The data, available at PATRIC (PathoSystems Resource Integration Center), provide novel information for unwinding the intricacies associated with Rickettsia pathogenesis, expanding the range of potential diagnostic, vaccine and therapeutic targets.
Highlights
Rickettsiae are a group of organisms belonging to the class Alphaproteobacteria, a large and metabolically diverse group of gramnegative bacteria [1,2,3]
Synteny and Phylogeny of Rickettsia Genomes Whole genome alignments for the ten analyzed Rickettsia taxa reveal highly conserved colinearity in six of the seven derived species with minimal gene rearrangements, most of which occur near the predicted origin of replication termination (Figure 2)
A conserved core rickettsial genome consisting of 731 orthologous groups (OGs) (51% of total predicted open reading frames (ORFs)) was identified, and a phylogeny was estimated from this core genome to allow for subsequent phylogenomic comparison of the remaining accessory genome
Summary
Rickettsiae are a group of organisms belonging to the class Alphaproteobacteria, a large and metabolically diverse group of gramnegative bacteria [1,2,3]. Within Alphaproteobacteria, the order Rickettsiales comprises three families: Holosporaceae, Anaplasmataceae and Rickettsiaceae [4], of which Rickettsia spp. are grouped in the latter, along with the monotypic genus Orientia, the scrub typhus agent [5]. Human rickettsial infections are known to cause many diseases, including epidemic typhus (R. prowazekii), murine typhus (R. typhi), murine typhus-like (R. felis), rickettsial pox (R. akari), Rocky Mountain spotted fever (R. rickettsii), Boutonneuse fever (R. conorii), and North Asian tick typhus (R. sibirica). These virulent species of rickettsiae are of great interest both as emerging infectious diseases [18] and for their potential deployment as bioterrorism agents [19,20]. The establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout the rickettsial tree (class 2 OG or C2OGs)
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