268
Anthology of Human Repetitive DNA
consensus sequences for other subfami-
lies. AluJo and AluJb are the two oldest
subfamilies that proliferated
65 million
y
e
a
r
sago
.A
luYi
sth
eyoung
e
s
tamong
major AluS subfamilies as it was retro-
transposed 5–30 million years ago. AluY
gave rise to a number of still younger
sub(sub)families of which the following
22 have been reported so far: AluYa1, Ya4,
Ya5, Ya8, Yb3a1, Yb3a2, Yb8, Yb9, Ybc3a,
Yc1, Yc2, Yd2, Yd3, Yd3a1, Yd8, Ye2, Ye5,
Yf1, Yf2, Yg6, Yh9, Yi6. At least some
of these sub(sub)families still contain el-
ements actively proliferating in human
populations, as indicated by their inser-
tion polymorphism. Among the largest
and best-studied active sub(sub)families
are AluYa5 and Yb8. However, some
of the smaller ones such as AluYb9,
Yc2, Yg6 and Yi6 are also of growing
interest in human population genetics
studies.
Densities of recently retroposed Alu
elements are about three times higher
on chromosome Y than on chromo-
some X, and about two times higher
than on autosomes. This indicates that
Alu elements are primarily retroposed
in paternal germlines. However, these
original chromosomal proportions change
very rapidly with time. The most strik-
ing long-term trend is the accumulation
of Alu elements in GC-rich and gene-
rich regions. At the same time L1 ele-
ments are predominant in AT-rich and
gene-poor regions. Given that newly retro-
transposed Alu and L1 elements are in-
serted into regions of similar GC content,
the evolution of the human genome is
characterized by massive subsequent re-
distributions of Alu repeats. The most
likely factor involved in the redistribu-
tions may be related to the different
patterns of postinsertion duplications and
deletions.
3.1.3
CR1-like Non-LTR Retrotransposons
CR1 is one of the most abundant and
widely
distributed
clades
of
non-LTR
retrotransposons that are present in the
genomes of birds, amphibians, Fshes,
reptiles,
invertebrates,
and
mammals.
Typically, autonomous CR1-like elements
are several kb long and contain two open
reading frames, OR±1 and OR±2, coding
for multidomain proteins. The OR±1p may
be involved in DNA/RNA binding, but
other interesting functions are also likely
(see below). The OR±2 protein includes the
APE and RT domains, which are distantly
similar to those identiFed in the L1 OR±2
protein. CR1-like elements do not generate
target site duplications.
3.1.3.1
L2 and L3 retroelements
Two hu-
man families of long interspersed repeats
called L2 and L3 were most likely am-
pliFed from active autonomous CR1-like
retroelements (±ig. 7). Given the high se-
quence diversity, their retrotransposition
probably occurred 200 to 300 million years
ago, long before mammalian radiation. To-
gether with the nonautonomous elements
described below, L2 and L3 represent
5%
of the human genome. Most of the pre-
served L2 and L3 copies are 5
0
truncated,
which, in addition to their very old age, im-
pedes reconstruction of their source genes.
±or example, the
3300-bp L2 consensus
sequence does not seem to contain the
OR±1 protein that is present in other CR1-
like retroelements. However, it is not clear
whether this is due to incomplete recon-
struction or because the active L2 source
gene lacked such a protein. The OR±1
protein is present in the L3 consensus
sequence, and it contains the esterase do-
main that is also present in the OR±1
proteins encoded by CR1-like elements
in birds, reptiles, and Fshes. Unlike L1,
neither L2 nor L3 elements are flanked
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