Biology Reference
In-Depth Information
L1 activity/mutations
Increase in the L1-asociated health risk? (cancer, aging ...)
Increase in the L1-asociated health risk? (cancer, aging ...)
Fixed low activity L1 loci
Fixed active L1 loci
Polymorphic low activity L1 loci
Polymorphic high activity “hot” L1 loci
Figure 6.3. Variation in the endogenous L1 activity in the human population. Due to the significant
number of the functional L1 loci in any human genome, the variation in the activity of
the same L1 locus among individuals, and the presence of polymorphic L1 loci that are
likely to be the most active L1s, there as an estimated 300-fold variation in the L1
activity among individuals in the human population. In a simplified model where there is
only one fixed and one polymorphic locus, the lowest predicted endogenous L1 activity
would be expected in individuals whose genomes harbor fixed L1 loci with low activity
(black bars). Individuals heterozygous (one blue/dark gray bar) or homozygous (two blue/
dark gray bars) for polymorphic low or high “hot” (green/light gray bars) activity L1 loci
are likely to experience a gradual increase in their total endogenous L1 activity.
A further augmentation in the endogenous L1 activity is expected in persons that
contain fixed active L1 loci (red/white bars) and a combination of these fixed L1s and
polymorphic low or high activity L1 loci. This gradient of L1 activity and most likely L1-
associated mutagenesis may be one of the contributing factors to the discrepancy in the
time of the onset and severity of human diseases associated with genomic instability
observed within human population.
mechanisms implemented by the host to combat the insult from TEs (see above
sections). A whole new chapter in human TE research has been opened by the
discovery of the intimate connection between the cellular DNA repair machin-
ery and L1-associated DNA damage (Gasior
et al.
, 2006; Gasior
et al.
, 2008;
Suzuki
, 2009). Thus, adequate DNA repair in individual genomes is
expected to control L1-associated damage. On the other hand, any decline in
the efficacy of the relevant DNA repair pathways, whether due to the loss of
function or to the decreased activity associated with certain genotypes, would
likely lead to an increased rate of accumulation of the L1-induced DNA damage.
et al.
