Biology Reference
In-Depth Information
identity that they share with their family consensus sequence. The presence of
interspersed sequence homology poses a serious challenge for the maintenance of
genomic integrity [reviewed in Hedges and Deininger, 2007]; this is particularly
the case for higher eukaryotes, such as mammals, that have larger genomes
containing higher repetitive element content (Lander
, 2001). The cellular
machinery involved in both recombination and DNA repair can be led astray by
homologous sequences present at nonallelic positions (Jasin, 2000). In the case
of recombination, this is most often observed in the context of NAHR. The
cellular protein machinery that initiates and monitors the strand invasion
process cannot always discern interspersed TE sequence homology from truly
allelic sequences. As a consequence of NAHR, genetic sequence can be dupli-
cated on one chromosome and lost on the other. In terms of TE/host interactions
this result can often have negative fitness consequences due to the loss or
alteration of critical genetic information. A significant number of human genetic
disorders have resulted from the nonallelic recombination of nearby Alu ele-
ments (Callinan and Batzer, 2006; Deininger and Batzer, 1999).
In addition to meiotic recombination, diploid (and higher ploidy)
organisms typically rely on the set of homologous chromosomes as templates
for the homology-driven (HR) DNA repair. The HR DNA repair system is
related to the recombination system and subject to the same limitations in
discerning true allelic sequence from interspersed homology. Products of mis-
aligned DNA repair—or repair events in which the only homologous templates
available are nearby repetitive sequences—can also generate rearrangements.
These rearrangements are, more often than not, intrachromosomal. Neverthe-
less, this same process can instigate interchromosomal rearrangements (Elliott
and Jasin, 2002; Elliott
et al.
, 2005).
While the focus of the deleterious effects of TEs has often centered on
the detrimental effects of unchecked insertional mutagenesis, there is evidence
that their ability to instigate nonallelic recombination may have an even great
impact on organismal short- and long-term fitness. To date, the larger fraction of
Alu-related genetic disease has been observed to arise through mutagenic recom-
bination (Callinan and Batzer, 2006; Deininger and Batzer, 1999; Elliott
et al.
,
2005). Song and Boissinot (2006) demonstrated evidence that negative selection
in the human genome principally acts upon TEs as a function of TE length. This
suggests that mutagenic NAHR, as opposed to insertional mutagenesis, may have
the more substantial negative consequences that retrotranspositional activity.
Similar evidence for the role of ectopic, nonallelic recombination in determin-
ing the fitness consequences of individual TE insertions was found in Drosophila
(Petrov
et al.
, 2003). In addition to causing disease, TE-associated reshuffling of
the host genetic material has had a significant impact on the host genome
architecture during the course of evolution (Han
et al.
et al.
, 2005, 2007, 2008;
Konkel and Batzer, 2010; Lee
et al.
, 2008; Xing
et al.
, 2009).
