278
Anthology of Human Repetitive DNA
Class III families of retroelements re-
constructed so far are nonautonomous,
including HERV-L, which was discovered
as the Frst representative of class III ele-
ments. ±or example, the HERV-L family
does not contain
env
, HERVL66 misses
gag
and protease, and HERVL68 does not
encode any proteins at all. The most abun-
dant Class III families are MaLRs (Mam-
malian apparent LTR retrotransposons)
and THE1 elements, which probably did
not encode any functional proteins at the
time of their activity. MaLRs (THE1) were
recently classiFed as members of Class
III based on the observation that some of
their noncoding sequences were derived
from HERV-L-like elements. HERV18 was
the Frst Class III element found to con-
tain
env
. Many different families of LTR
retrotransposons are still represented by
their LTRs only. As shown in Tables 4 and
6, these families were reliably assigned to
their proper classes based on similarities
to LTRs from classiFed retroelements.
Class I LTR retrotransposons (Table 4)
include dozens of nonautonomous fami-
lies that are members of the same group,
also called the MER4 or MER4I group af-
ter the MER4 element that was discovered
over a decade ago and later identiFed as
an LTR flanking the internal portion of
a retrovirus-like element (MER4I). Other
Class I families of LTR retrotransposons
were discovered and classiFed on the ba-
sis of their sequence similarity to MER4I.
All these families are characterized by 4-
bp target site duplications. Analogously to
MaLR and THE1 elements, the originally
discovered MER4I-like retrotransposons,
do not code for any proteins. ±urther-
more, the human genome also harbors
autonomous Class I families whose mem-
bers were ancestral to nonautonomous
MER4I-like elements. ±or example, the in-
ternal portion of the PRIMA4 autonomous
retrovirus is similar to the entire MER4I
sequence; even their LTRs are similar.
Analogously, the autonomous PRIMA41
retrovirus is an ancestor of the MER41
family of MER4I-like nonautonomous el-
ements. Class I elements were involved
in vigorous multiple recombinations be-
tween RNA copies of different retroviruses.
As a result, many Class I families are
chimeras composed of parts that came
from retroviruses dissimilar to each other,
for example,
Harlequin
.
Class III and Class I elements were
probably engaged in extensive comple-
mentation, meaning that various families
mutually assisted each other by shar-
ing necessary enzymatic and packaging
activities. ±or instance, the RNA of nonau-
tonomous proviruses can be copackaged
into functional viral cores produced by
autonomous LTR retroelements and ex-
ogenous retroviruses. These viral cores can
be released from the host cell and can
infect other cells. Given the low Fdelity
of reverse transcription (
10
5
per nu-
cleotide per cDNA molecule), the original
nonautonomous retrovirus can be dramat-
ically transformed after multiple rounds
of reverse transcription and intercellular
migrations. As a result of such transfor-
mation, the similarity between the original
provirus and the transformed retrotrans-
poson can wane rather fast.
Human Class II elements are repre-
sented by 11 families (Table 5) with ages
ranging from
35 million to less than
5 million years. The oldest Class II family
is HERVK22. On the other hand, some
HERVK10 elements are polymorphic in
the human population, and contain nearly
intact OR±s coding for the standard retro-
viral proteins. In addition to the standard
proteins, some HERVK elements encode
dUTPase and K-Rev. The latter is a 105-aa
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