Biology Reference
In-Depth Information
type may have a threshhold for tolerable L1 expression. This limit may reflect the
ability of cells to deal with the TE-induced genomic insult. As a result, un-
planned upregulation of endogenous L1 expression may result in elimination of
normal—and even some cancerous—cells through apoptosis (Belgnaoui
et al.
,
2006; Bourc'his and Bestor, 2004) or senescence (Belancio
et al.
, 2010b; Wallace
et al.
, 2008b). Thus, the collective TE expression and activity in any given cell
type is likely determined by the combination of the factors established to limit
TE expression and by the amount of the TE-associated toxicity that can be
endured by these cells.
D. Genetic variation and polymorphism of TE loci
Significant progress has been made in understanding the complexity associated
with the fact that TEs are families of elements individual members of which are
distributed throughout the genome and often harbor significant sequence varia-
tions relative to the rest of the group. Several causes are currently known to
contribute to this variation. One of them is infidelity of the L1 RT which is
estimated to introduce at least one mutation per every 6000 incorporated
nucleotides. This corresponds to the size of the human L1. The biological
implication of this finding is that every
full-length L1 insertion generated
by the same active L1 locus has a high likelihood of containing at least one point
mutation. Another reason for diversity among family members is the natural
accumulation of mutations within any given TE locus due to genomic drift.
Other frequent on-arrival or time-inflicted changes include significant
alterations in the length of the polyA tail present at the end of each element.
Longer A-tails are associated with younger and more active Alu and L1 elements
(Lander
de novo
, 2002). However, because of the difference
in the generation of this A-tail between L1 and Alu elements, the encoded
length of the polyA stretch has a particularly dramatic effect on the rate of Alu
retrotransposition (Comeaux
et al.
, 2001; Roy-Engel
et al.
, 2002). An A-tail of
an individual element can shrink or grow by 10s of nucleotides during, or shortly
following retrotransposition. This translates in the several fold difference in its
retrotransposition efficiency among individual insertions (Comeaux
et al.
, 2009; Roy-Engel
et al.
et al.
, 2009;
Dewannieux
, 2002). The same consequences for Alu
retrotransposition can also arise from mutations interrupting the continuity of
the A-tail (Comeaux
et al.
, 2003; Roy-Engel
et al.
, 2009). The variations generated during transposition
along with accumulated random mutations influence the relative activity of
individual TE loci (Aleman
et al.
, 2008). The disparity in
the efficiency of retrotransposition is observed not only among the loci of the
same TE family but also between the same TE locus isolated from different
individuals (Brouha
et al.
, 2000; Bennett
et al.
, 2006). Depend-
ing on the presence of modifying mutations, the same insertion locus could be
et al.
, 2003; Lutz
et al.
, 2003; Seleme
et al.
