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Vol. 11, Issue 8, 1321-1322, August 2001
INSIGHT/OUTLOOK
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Although the potential of transposable elements (TEs) to produce
genomic rearrangements, such as inversions and
translocations, has been appreciated for some time from the results of
laboratory experiments, estimates of the frequency and evolutionary
importance of such events in natural populations have been difficult to
come by. Now, with the ability to obtain nucleotide sequence data on a
large scale, we are starting to learn about the nature and frequency of
TE-induced changes in the structure of their host genomes. Not only is
direct evidence being provided to support predictions that TEs can
initiate chromosomal rearrangements by ectopic recombination and other
mechanisms, but surprising examples of massive local genomic
instability are being reported that were not predicted by earlier
models of TE behavior. In this issue, a remarkable example of an
unprecedented degree of genome restructuring is reported in a study of
the breakpoints of a TE-induced inversion in Drosophila
buzzatii (Caceres et al. 2001
).
Genomic Rearrangements are Abundant in Drosophila
The unusually rich inversion polymorphism seen in many species of
the Drosophila genus provides fertile ground for study of the
mechanisms involved in generating genomic rearrangements. The rate of
chromosomal reshuffling in Drosophila appears to be higher
than that of any other animal or plant taxon that has been studied
similarly (Ranz et al. 2001). D. buzzatii is a cactophylic species associated with host plants of the Opuntia genus. The species originated in Argentina and is distributed widely in South America. Recently this species colonized the Mediterranean region of
the Old World and Australia. Chromosome 2 of D. buzzatii is polymorphic for two major structural configurations that are found throughout the species range. The standard ancestral configuration, 2st, has a gene order consistent with that of other closely
related species. The second form, 2j, was derived from the
standard form and contains an inversion of a centrally located segment
that represents approximately one-third of the euchromatic fraction of
that chromosome. In earlier work with the D. buzzatii system, Caceres et al. (1999) elegantly implicated ectopic recombination between two members of a foldback (FB) transposable element family, named Galileo, as the mechanism of induction of the
2j inversion. They not only showed the presence of the two
Galileo elements at the inversion breakpoints (BPs), but also
identified small direct duplications of host DNA (the signatures left
by a TE insertion) which provided direct proof of inversion induction
by the Galileo elements. Now, in a followup study, they report
a detailed molecular analysis of a 7.1-kb stretch of DNA surrounding
the inversion BPs in multiple lines of flies sampled from natural
populations throughout the species range. Such a detailed analysis
allowed a reconstruction of the evolutionary sequence of events that
occurred in these regions.
Massive Reshuffling in a Short Period of Evolutionary Time
The results of this study are remarkable in two ways. They
demonstrate, first, the unprecedented frequency and complexity of
molecular rearrangements in the relatively short chromosomal regions
surrounding the inversion breakpoints and, second, the remarkable
rapidity of these changes on an evolutionary timescale. The
rearrangements identified in 30 2j chromosomes included 22 insertions of 10 TEs, 13 deletions, one duplication, and an internal inversion. The frequency of insertions (per kb per chromosome) was at
least two orders of magnitude higher than those observed in earlier
studies of euchromatic regions of D. melanogaster and other
Drosophila species. Furthermore, the use of multiple lines of
flies from natural populations by Caceres et al. (2001) allowed detailed characterization of the complex molecular events that occurred
in the hotspot regions.
The average rate of nucleotide substitution of unique DNA sequences
immediately adjacent to the inversion BPs was found to be significantly
lower in the inverted 2j chromosomes compared with that for
the 2st chromosomes. On this basis, the observed changes in
the 2j chromosome were estimated to have taken place in
<84,000 years. This contrasts with 485,000 years that was estimated as
the age of the 2st chromosomes. The rapidity of reshuffling in
the 2j breakpoint regions is even faster than that reported for the adh1 region of maize, in which an intergenic region
more than doubled in size, mainly during the last three million years, due to the activity of retrotransposons (SanMiguel et al. 1998).
What is the Mechanism of Hotspot Induction?
The absence of insertions and structural rearrangements in the
homologous regions of the uninverted (2st) chromosome, in the D. buzzatii study, possibly implicates the inversion as the
most likely explanation for the rearrangement hotspots. Although it is
expected that TEs will accumulate around inversion BPs because of the
protection afforded by the reduction of recombination in these regions
(Montgomery et al. 1987), a number of observations suggest that other
factors are also involved. These include: (1) the restriction of
rearrangements to a very short region around the BPs, (2) the absence
of retrotransposons, the most common type of Drosophila TE, in
the hotspot regions, (3) the absence of insertions in homologous
regions of uninverted chromosomes, and (4) the presence of deletions
and other rearrangements in the hotspot regions, in addition to the
insertions. The authors favor an alternative hypothesis for hot spot
induction, namely the presence of the initial insertions of
Galileo. Members of the FB TE family are known to be
associated with unstable mutations and chromosomal rearrangements, as
well as insertions nested within one another (SanMiguel et al. 1996).
A predominant feature of the region under discussion is the frequent
nesting of new TE insertions within earlier insertions. This is
reminiscent of the behavior of LTR retrotransposons that are found most
frequently in methylated, presumably locally heterochromatic regions of
the adh region of the maize genome, often in nested clusters
(SanMiguel et al. 1996). Accumulation in nested clusters is also
observed in the telomeric regions of some species, for example, the
silkworm Bombyx mori (Takahashi et al. 1997) and the green
alga Chlorella vulgaris (Higashiyama et al. 1997), and in
nested regions elsewhere in the genome, sometimes referred to as TE
"landing pads" in yeast (Kim et al. 1998).
Hotspot Insertion Profiles do Not Represent Drosophila TE Diversity
Of particular interest is the observation that the TEs identified
in the hotspot regions adjacent to the inversion BPs are far from being
representative of the diversity of Drosophila elements. Class
II elements that transpose using a DNA intermediate are overwhelmingly
represented in the identified insertions. These include the newly
discovered families of FB elements (Galileo, Kepler and Newton) and representatives of the
hAT (hobo, Activator, Tam)
superfamily of elements. The abundance of FB elements provides some explanation for the present observations because of the known high
level of instability and recombinogenic properties of these elements
(Hoffman-Liebermann et al. 1985).
Interestingly, no representatives of the Class I retroelements were
identified clearly in the sampled region. This is surprising given the
abundance of these elements in Drosophila genomes. However, ISBu-1, one of the elements newly discovered in this study,
has subsequently been identified as a member of a novel class of
abundant Dipteran mobile elements named mini-me (Wilder and
Hollocher 2001). These elements appear to represent a new subclass of
retroposons that have the potential to provide a prolific source of
microsatellite variation in many Drosophila species. In fact,
the presence of the ISBu-1 insertion in the D. buzzatii
2j chromosome was cited as a prime example of the recent mobility
of some members of this new subclass of TEs (Wilder and Hollocher 2001).
Remaining Questions
How are we to assess the overall evolutionary significance of these
results in D. buzzatii? Are the D. buzzatii results
an interesting, but rare, anomaly? This species belongs to the D. repleta group of the Drosophila subgenus. The second
chromosome of repleta group species is homologous to the
3R chromosome of D. melanogaster. The latter species
is a member of the subgenus Sophophora which diverged from
the Drosophila subgenus 40-62 million years ago. So far, no
reports of any genomic regions exhibiting rapid evolution comparable to
those now reported in D. buzzatii have been made following the
sequencing of the genome of D. melanogaster (Adams et al.
2000) With the rapid appearance of new sequence data predicted in the
near future, intra- and inter-specific genomic comparisons combined
with enhanced tools for finding novel repetitive DNA, we should soon
start to have some of the answers to these and related questions.
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ACKNOWLEDGMENTS |
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This work was supported by National Science Foundation Grant DEB-9815754.
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FOOTNOTES |
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1 Corresponding author.
E-MAIL kidwell{at}azstarnet.com; FAX (520) 621-9190.
Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.201201.
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