This group of elements was named after the directly repeated insertion sequences in transposon Tn6 (31). Historically, several of these elements were attributed individual IS numbers and have subsequently been determined to be identical. Many have been found as part of compound transposons. Several distinct family members have been shown to transpose. The putative Tpases are very closely related and show identity levels ranging from 40 to 94%. They generally range in length from 789 bp (IS257) to 880 bp (IS6100). Note that one isolate however, IS15, corresponds to an insertion of one iso-IS6 (IS15D) into another (481). Although it has been included in the family based on similarities of its terminal IRs (Fig B.), IS466 from Streptomyces coelicolor is 1628 bp in length and the Tpase orf has yet to be determined. All carry short related (15-20 bp) terminal IRs and generally create 8 bp direct target repeats. No marked target selectivity has been observed (333). Interestingly sequences identical to the Mycobacterium fortuitum IS6100 have recently been identified as part of a plasmid-associated catabolic transposon carrying genes for nylon degradation in Arthrobacter sp. (236), from the Pseudomonas aeruginosa R1003 plasmid (181), and within the Xanthomonas campestris transposon Tn5393b (460). Similar copies have also been reported in Salmonella enterica (typhimurium) (54) and on plasmid pACM1 from Klebsiella oxytoca (AF107205).This suggests a relatively recent horizontal dissemination.
IS257 (also known as IS431) has played an important role in sequestering a variety of antibiotic resistance genes in clinical isolates of methycillin resistant Staphylococcus aureus (MRSA). It provides an outward oriented promoter which drives expression of genes located proximal to the left end. Moreover, both left and right ends appear to carry a –35 promoter component which would permit formation of hybrid promoters on insertion next to a resident –10 element (442, 31a, 198a.)
In the case of IS26, an open reading frame is transcribed from a promoter located within the first 82 bp of the left end. It stretches across almost the entire IS, is required for transposition activity (333), and the predicted amino acid sequence of the corresponding protein exhibits a strong DDE motif . Translation products of this frame have been demonstrated for IS240 (109) and IS26 (Vögele, pers. comm.). Little is known concerning the control of Tpase expression although transposition activity of IS6100 in Streptomyces lividans (445) and IS26 in Escherichia coli (Vögele, pers. comm.) indicates that transposition activity is significantly increased when the element is placed downstream from a strong promoter. Insertion of one member, IS257, can result in activation of a neighboring gene using both a hybrid promoter and an indigenous promoter (442).
Where analysed, members of the IS6 family give rise exclusively to replicon fusions (cointegrates) in which the donor and target replicons are separated by two directly repeated IS copies (e.g. IS15D, IS26, IS257, IS1936). Transposition of these elements is therefore presumably accompanied by replication. Following cointegration, a resolution step is required to separate donor and target replicons and to transfer the transposon to the target replicon. Recombination between directly repeated ISs necessary for this separation occurs by homologous recombination and requires a recombination proficient host ( Fig B.).
An interesting similarity has been observed with a 4,904 bp element isolated from the filamentous cyanobacterium Fremyella diplosiphon (Tn5469 (IS5469), (242)). This relatively long element carries three consecutive orfs. The protein coded by the first and longest frame, TnpA, is 909 residues in length compared to the IS6 family Tpases of between 220 and 260 residues. While TnpA contains an N-terminal region which exhibits significant conservation with the IS6 Tpases (27 of 80 conserved residues over approximately 220 residues) this region does not carry the DDE motif. On the other hand, a clear DDE motif resembling the Tpases of Tn5090 (Klebsiella aerogenes plasmid R751 (387)) and of the relatively complex transposon Tn552 (Staphylococcus aureus (415)) is located in the C-terminal region. Moreover, the ends of Tn5469 exhibit a strong similarity to those of the IS6 family members. This raises the possibility that recognition of the ends is determined by the IS6-like N-terminal region while catalysis is governed by a Tn552-related recombinase.
Mahillon J. and
Chandler M.
(1998)
Microbiology
and Molecular Biology
Reviews.
62 : 725-774
Chandler, M. and Mahillon, J.(2002) Insertion Sequences Revisited
Mobile DNA II Edited by N.L., Craig et al.
ASM
Press 305-366
with permission of American Society of Microbiology the 10-26-01.
Last modification : December 19 2001