Biology Reference
In-Depth Information
highly active in one individual but quiescent in another. This phenomenon was
first reported for L1 elements and is likely to be the case for Alu and SVA
elements as well.
Regardless of their origin, mutations within TE sequences can have a dual
effect on their activity, as already alluded to above regarding A-tail length. On one
hand, these mutations can inactivate or reduce the activity of one of the important
L1 protein functions required for retrotransposition of L1 or all three human non-
LTR retrotransposons. They can also disrupt other critical elements, such as
promoter activity, RNA folding, RNA/protein, protein/protein interactions, etc.,
each one of which may eliminate or diminish retrotransposition. On rare occa-
sions, however, these mutations may potentially lead to a beneficial change in any
of the above mentioned activities or interactions leading to an improvement in
retrotransposition. L1 elements with highest retrotransposition potential are
referred to as “hot” elements (Brouha
,2003). “Hot” Alu and SVA elements
are likely present in the human genome as well, but are yet to be characterized.
TE loci in any given human genome can be either fixed or polymorphic
in the population. Fixed loci are evolutionary older and are present in all
members of the population (excluding rare genomic rearrangement events that
can remove a TE locus after fixation took place). Because of their evolutionary
age they are more likely to harbor inactivating mutations and, as a result, have
lost their activity (Aleman
et al.
, 1996).
The vast majority of TE loci found in the human genome is represented by the
fixed-present elements. Polymorphic TE loci are found only in the subset of
individuals in the population and their allele frequencies may vary significantly
among the populations of different origin (Cordaux
et al.
, 2000; Lander
et al.
, 2001; Moran
et al.
et al.
, 2007; Wang
et al.
,
2005; Watkins
, 2003). Polymorphic TE loci are likely to be the most active
and they are expected to account for the bulk of TE activity in any given genome
(Beck
et al.
et al.
, 2010; Brouha
et al.
, 2002, 2003; Ewing and Kazazian, 2010; Huang
et al.
, 2010). Initial screening suggested that polymorphic L1s
are rare and a very small number of L1 loci are “hot” (Brouha
, 2010; Iskow
et al.
, 2002, 2003).
Advances in the whole genome analysis significantly broadened the estimation
of the polymorphic L1 loci per genome. In fact, the most recent estimation is that
any two human genomes differ on average by 285 sites with respect to presence or
absence of L1 insertion (this includes truncated and full-length L1s; Ewing and
Kazazian, 2010). Additionally, over half of the identified polymorphic L1s
exhibit levels of activity that can be characterized as “hot” (Beck
et al.
, 2010).
The observation that there is most likely a group of polymorphic TE loci that are
private, that is unique to individual genomes, further expands the TE-associated
genetic diversity between individual human genomes (Beck
et al.
, 2010; Ewing
and Kazazian, 2010). There is also a significant increase in the L1-associated
variation between normal and some cancer genomes (Iskow
et al.
, 2010). These
findings strongly support that there is a considerable interindividual genetic
et al.
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