Anthology of Human Repetitive DNA
277
The replication is completed when RT
synthesizes the entire plus and minus
DNA strands. The fnal product is a
linear duplex DNA.
Life cycle of LTR retrotransposons
The liFe
cycle oF an LTR retrotransposon starts
with the transcription oF its provirus
copy
integrated
in
the
genome. The
resulting mRNA is transported From the
nucleus to the cytoplasm, where it is
translated. Usually, reverse transcription
oF the proviral mRNA occurs in the
viral particles
in
the
cytoplasm. The
resulting cDNA is then transported back
to the nucleus, together with the retroviral
integrase where the integrase inserts the
cDNA into the host genome, producing
a new provirus flanked by identical LTRs
and short TSDs.
Subsequent homologous recombination
between the LTRs may result in elimi-
nation oF the provirus with the exception
oF a solo LTR (±ig. 10). The number oF
endogenous retroviruses that retain their
internal portions flanked by both LTRs is
about ten times smaller than the number
oF solo LTRs. ThereFore, recombination
between the flanking LTRs is a signifcant
Factor in elimination oF LTR retrotrans-
posons. Gene conversion between LTRs
can also occur at a very low rate. ThereFore,
the average divergence between provi-
ral LTRs does not adequately reflect the
age oF the corresponding Family oF LTR
retrotransposons.
RNA recombination of LTR retrotransposons
LTR
retrotransposons
copackage
two
copies oF their RNAs, which can recom-
bine with each other, in the same viral
particle. Two RNAs representing essen-
tially distinct LTR retrotransposons can
also be copackaged together iF they share
similar
ψ
packaging signals. Retroviral re-
combination is usually mediated by the
RNA template switch that occurs during
minus-strand DNA synthesis, when RT
is paused by a break in the reverse tran-
scribed RNA. The RT pausing can also be
caused by a specifc secondary structure oF
the RNA template and by internal repeats.
Characteristics of human LTR retrotrans-
posons
The most abundant and ancient
group oF LTR retrotransposons preserved
in the human genome are class III retro-
transposons (Table 6). ±or example, the
HERVL16 and HERVL33 Families are
more than 200 million years old. Despite
their high abundance, they have remained
undetected For a long time due to their ex-
tensive modifcation by mutations. Most
Fig. 10
Formation of a solo
LTR through the illegitimate
recombination between
proviral LTRs.
Recombination
Heteroduplex formation
+
Solo LTR
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