Rearrangement analysis of multiple bacterial genomes

Abstract

Background: Genomes are subjected to rearrangements that change the orientation and ordering of genes during evolution. The most common rearrangements that occur in uni-chromosomal genomes are inversions (or reversals) to adapt to the changing environment. Since genome rearrangements are rarer than point mutations, gene order with sequence data can facilitate more robust phylogenetic reconstruction. Helicobacter pylori is a good model because of its unique evolution in niche environment.

Results: We have developed a method to identify genome rearrangements by comparing almost-conserved genes among closely related strains. Orthologous gene clusters, rather than the gene sequences, are used to align the gene order so that comparison of large number of genomes becomes easier. Comparison of 72 Helicobacter pylori strains revealed shared as well as strain-specific reversals, some of which were found in different geographical locations.

Conclusion: Degree of genome rearrangements increases with time. Therefore, gene orders can be used to study the evolutionary relationship among species and strains. Multiple genome comparison helps to identify the strain-specific as well as shared reversals. Identification of the time course of rearrangements can provide insights into evolutionary events.

Keywords: Gene order; Genome rearrangements; Helicobacter pylori; Reversals.

Fig. 1

Workflow of the program. a Gene orders from 1 to n. b Consensus gene order created by identifying the most common upstream and downstream gene using the majority rule. Arrows (blue: majority, red: rare) indicate the upstream and downstream genes. c All genes reordered according to the consensus. d Breakpoints (red vertical lines) identified in gene orders of all strains. e First, the rare reversals are identified and fixed. Then similar strains are merged. Merging is repeated until no strains can be merged. Shared reversals are obtained

Fig. 2

Phylogenetic tree based on the core genes of 73 H. pylori strains. Colored boxes represent the geographical region of the strains (Yellow: East Asia, Red: South America, Purple: North America, Green: Europe, Brown: Africa, Light Blue: India, Grey: Australia). Black arrows indicate strains with no geographical information

Fig. 3

Distribution of inversions. a Different color of regions in the map correspond to the number of strains included in this analysis. Pie chart along each region shows the distribution of the inversions in strains of that region (Additional file 12: Table S7). b R1-R23 and R24-R41 were identified as shared and strain-specific inversions, respectively. Among the shared inversions, R17-R23 were region-specific

Fig. 4

Inversion-based phylogeny. Labels beside the branches represent the inversions occurred in the strains (Additional file 8: Table S4). Strains names are colored representing the geographical location (same as Fig. 2). Strains name in black color show the strains with no geographical information. Legend on the right side indicate the reversals shared among multiple strains. * ignoring single gene transposition, ** ignoring single gene transposition and 2 gene inverse transposition, *** ignoring single gene transposition, 2 gene inverse transposition and 3 gene deletion