The influence of different IS on genome
architecture will depend not only on their levels of activity but also on the
type of target into which they insert. It was initially believed that TE show
no or only low sequence specificity in their target choice. For example IS630 and the eukaryotic Tc/mariner families (Tellier, et al., 2015) both
require a TA dinucleotide in the target (Plasterk,
1996, Feng & Colloms, 2007) while others such as the IS200/IS605 and IS91 families require short tetra- or penta-nucleotide sequences (Mendiola & de la Cruz, 1989, Guynet, et al., 2009). Yet others, such
as IS1 and IS186 (of the IS4 family), show some regional
, et al., 1980, Meyer, et al., 1980, Sengstag, et al., 1986).
Although, from a global
genome perspective, insertion may appear to occur without significant sequence
specificity, accumulation of more statistically robust data has uncovered
rather subtler insertion patterns revealing that several TE use rather shrewd
mechanisms in choosing a target. For example, there is some indication from the
public databases suggesting that IS density is generally significantly higher
in conjugative bacterial plasmids than in their host chromosomes with the
exception of special cases in which the host has undergone IS expansion. Such
plasmids are major vectors in lateral gene transfer and are important vectors
in IS transmission (as well as in transmission of accessory traits such as
resistance to antibacterials). Some TE, including IS, appear to be attracted to
replication forks (Peters & Craig, 2001,
Ton-Hoang, et al., 2010) and
show a strong orientation bias indicating strand preference at the fork (Hu & Derbyshire, 1998, Peters & Craig, 2001,
Ton-Hoang, et al., 2010). Moreover,
in certain cases, insertion may target stalled replication forks (He, et al.,
2015). A link between replication (in this case, replication origins)
Drosophila(Spradling, et al., 2011).
For example, transposon
Tn7 has two modes of transposition:
in one, which uses the Tn7-encoded target protein TnsD, a specific sequence
within the highly conserved glmS is
recognized and insertion occurs next to this essential gene (Craig, 2002); in the second, which uses a more
general targeting protein, TnsE, insertion occurs into replication forks
directed by interactions with the b-clamp (Parks, et al., 2009). This latter pathway results in a strong
orientation bias of Tn7 insertions,
consistent with insertion into the lagging strand of the replication fork
formed during conjugative transfer. Although studies with IS are less advanced,
a similar orientation bias was observed with IS903 (Hu & Derbyshire, 1998),
suggesting that it too may use the b-clamp in directing insertions. It seems probable that many other IS use
this type of protein-protein interaction.
A second example of
specialized target choice was observed in members of the IS200/IS605 family. These transpose using a
strand-specific single strand intermediate and insertion occurs 3' to a tetra-
or penta-nucleotide on the lagging strand (Ton-Hoang, et al., 2010, He, et al., 2015). Clear vestiges of this specificity can
still be detected in a large number of bacterial genomes where the orientation
of insertion is strongly correlated with the direction of replication. There
are clearly incidences of insertion in the "wrong" orientation but many of
these may be explained by post insertion genome rearrangements involving
inversions. This would place the "active" strand of the IS on the lagging
rather than on the leading strand. Interestingly, those IS which are not
oriented in the "correct" orientation with respect to replication are almost
certainly inactive and unable to transpose further (Ton-Hoang, et al., 2010).
Other examples of
sequence-specific target choice have been described. IS1, for example, shows a preference for regions rich in AT whereas
the transposon TnGBS (an ICE from Steptococcus agalactiae) and members
of the closely related ISLre2 family show a preference for insertion
15-17 bp upstream of σA promoters (Brochet, et al.,
2009, Guerillot, et al., 2013). Targeting of upstream regions of
transcription units has also been extensively documented for certain eukaryotic
transposons (e.g.(Qi, et al., 2012)).
characteristics or secondary structures are another feature which can attract
certain TE. Changes in topology induced by the nucleoid protein, H-NS, for
example, may explain the effects of H-NS mutants on the target choice of IS903 and Tn10 (IS10) (Swingle, et al., 2004, Haniford & Ellis,
of the IS110, IS3 and IS4 families are examples of IS which insert into
potential secondary structures such as Repeated Extragenic Palindromes (REP)(Clement, et al.,
1999, Wilde, et al., 2003, Tobes
& Pareja, 2006, He, et al., 2015), integrons (Tetu & Holmes, 2008, Post & Hall, 2009) or even the ends
, et al., 1991, Partridge & Hall, 2003).
Some transposons such as
Tn7 in Escherichia coli (Peters & Craig, 2000) and Tn917 in Bacillus subtilis (Shi, et al., 2009), Enterococcus faecalis (Garsin, et al.,
2004) and Streptococcus equi (but
not in Listeria monocytogenes or Streptococcus suis) (Slater, et al.,
2003) also show
a preference for integration into the replication terminus region and sites of DNA breakage may also attract
insertions (Peters & Craig, 2000).
Interestingly, an analysis of incorporation of "self-DNA" by a CRISPR system in
E. coli showed a preference for trapping DNA from the terminus region of the
chromosome (Levy, et al., 2015), mimicking the target preference of Tn7. It
remains to be seen whether any IS has adopted these types of target preference.
In addition, IS21,
IS30 and IS911 have all been observed to insert close to sequences which resemble their
own IR (Reimmann & Haas, 1987, Prere, et al., 1990, Olasz, et al., 1997, Loot, et al., 2004). Although these IS are members of different
families, they have in common the formation of a dsDNA excised circular
transposon intermediate with abutted left and right ends (Chandler, et
al., 2015). Insertion next to a resident "target" IR such that IR of
the IS are abutted "head-to-head" presumably reflects the capacity of the Tpase
to form a synaptic complex between one IR present in the transposon circle and
the target IR. This type of structure is extremely active in transposition and
will continue to generate genome rearrangements.
These examples represent
only a small part of the literature concerning factors influencing target
choice but serve to illustrate the impact this can have on genomes.
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