Bacterial insertion sequences: their genomic impact and diversity

Abstract

Insertion sequences (ISs), arguably the smallest and most numerous autonomous transposable elements (TEs), are important players in shaping their host genomes. This review focuses on prokaryotic ISs. We discuss IS distribution and impact on genome evolution. We also examine their effects on gene expression, especially their role in activating neighbouring genes, a phenomenon of particular importance in the recent upsurge of bacterial antibiotic resistance. We explain how ISs are identified and classified into families by a combination of characteristics including their transposases (Tpases), their overall genetic organisation and the accessory genes which some ISs carry. We then describe the organisation of autonomous and nonautonomous IS-related elements. This is used to illustrate the growing recognition that the boundaries between different types of mobile element are becoming increasingly difficult to define as more are being identified. We review the known Tpase types, their different catalytic activities used in cleaving and rejoining DNA strands during transposition, their organisation into functional domains and the role of this in regulation. Finally, we consider examples of prokaryotic IS domestication. In a more speculative section, we discuss the necessity of constructing more quantitative dynamic models to fully appreciate the continuing impact of TEs on prokaryotic populations.

Keywords: diversity; evolution; genome; insertion sequence; mechanism.

Figure 1

Distribution of IS families in the ISfinder database. The histogram shows the number of IS of a given family, as defined in the text, in the ISfinder database (June 2013). The horizontal boxes indicate the number and relative size of different subgroups (see Table 1 for the subgroups names) within the family. They are grouped by colour to indicate the type of Tpase used: DDE, blue; undetermined, purple; DEDD, green; HUH, red; Serine, orange.

Figure 2

IS expansion, elimination and genome ‘streamlining’. The figure shows schematically from left to right events leading to the evolution of host‐dependence in bacteria. (i) The parental (ancestral) chromosome including a low number of resident IS (red arcs). Note that the entire genome might also include transmissible plasmids carrying their own IS load, which can in principle undergo transposition into the chromosome. (ii) IS expansion occurs as a result of isolation and the formation of population bottlenecks within a host organism. This is accompanied by mutation promoted by insertion of new IS copies and by their related transposition activities of deletion and rearrangement. These genome rearrangements can also occur by homologous recombination between identical IS copies. (iii) With time IS will have a tendency to undergo deletion with adjacent DNA sequences in the absence of direct selection. This leads to a reduction in genome size. (iv) Eventually, extensive deletion will lead to the generation of nonautonomous IS fragments and their elimination. (vi) This gives rise to streamlined, IS ‘free’ genomes which may become ‘reinfected’ by IS on rare contact with other, IS‐carrying strains or infection by IS‐carrying bacteriophage (v).

Figure 3

Organisation of the IS 200/IS 605 family. (i) IS 200 group with tnpA alone: examples include IS 200 (Salmonella typhimurium, Escherichia coli), IS 1541 (Yersinia pseudotuberculosis, Yersinia pestis), IS 1469 (Clostridium perifringens) and ISW 1 (Wolbachia sp.). (ii) IS 605/IS 606 type with tnpA and tnpB in a divergent orientation: IS 605, IS 606 (Helicobacter pylori); ISL jo5 (Lactobacillus johnsonii). (iii) IS 8301 type with nonoverlapping tnpA and tnpB orfs in the same direction: ISD ra2 (Deinococcus radiodurans), ISH 1‐8 (Halobacterium), ISE fa4 (Enterococcus faecium), IS 1253 (Dichelobacter nodosus). (iv) IS 608 with overlapping tnpA and tnpB: IS 608 (Helicobacter pylori). (v) IS 1341 (Thermophilic bacterium) group with tnpB alone. Left and right are represented as hairpin structures in red and blue, respectively. Orfs are indicated as boxes with arrowheads (showing the direction of translation). tnpA is shown in red and tnpB in blue.

Figure 4

tIS: IS with passenger genes. The IS is represented as a rectangle with flanking direct repeats (DR) in red and terminal inverted repeats in blue (triangles). The Tpase orfs are shown in dark blue and passenger genes in green. (a) Organisation of a classical IS66 family member and of the ISBst12 group. The ‘accessory’ genes tnpA and tnpB are shown in red and orange, respectively. (b) An IS1595 family member with noncoding DNA. (c) A tIS 66 with a single orf downstream of the Tpase. (d) IS66 and IS4 tIS with passenger gene(s) upstream of the Tpase. (e) An IS1595 family tIS with upstream and downstream passenger genes.

Figure 5

Relationship between IS, tIS and MITES. (a) The (hypothetical) relationship between different IS derivatives (shown as light blue boxes). Horizontal arrows indicate open reading frames encoding the Tpase (dark blue), passenger genes (orange). The terminal inverted repeats are shown as darker blue triangles. Examples of IS families which include such derivatives are indicated at the bottom of the panel. (b) The particular case of MITES derived from IS 200/IS 605 family members. The IS ends with their essential secondary structures are shown in red (left end) and blue (right end). The colour scheme is as described for (a). The TnpB accessory gene is shown as a green horizontal arrow.

Figure 6

Domain organisation of transposases of the DDE family. The relative positions of the potential ZF, HTH, LZ and the ‘DDEK/R’ catalytic motif are indicated from left to right as light blue boxes. The figure illustrates the N‐terminal and C‐terminal extension of the different transposase examples. (a) Classical IS 1 with frameshift. The position of the frameshift window which is used to generate InsAB is indicated. (b) IS 1 without frameshift and the ISM hu11 group showing the deletion of the ZF, the C‐terminal extension and the increased spacing between the second (d) and (e) residues. (c) The IS 1595 family showing the classical IS 1595 group and the IS 1016 group which does not carry the N‐terminal ZF. (d) The IS 3 family including members with and without the translational frameshift. (e) The closely related IS 481 family which lack the N‐terminal HTH domain and exhibit an additional C‐terminal domain.