Anthology of Human Repetitive DNA
267
relative to the left monomer, and the
monomers are separated by the A-rich
central region. The right monomer also
contains a 3
0
-oligo-dA-rich tail (or polyA
tail), usually 20 to 30 bp long. Free Alu
monomers such as FLA, FLAM, and
FRAM were very active during the early
era of Alu evolution, and at least one
of them, BC200, has been recruited as
a regulated gene expressed in the brains of
higher primates.
Probably around one hundred Alu el-
ements out of one million appear to be
currently participating in retrotransposi-
tion. It is unclear why Alu retroposition is
con±ned to this limited number of ‘‘mas-
ter’’ or ‘‘source’’ genes. One often invoked
explanation is that most retroposed ele-
ments remain untranscribed. For example,
pol III transcription depends on flank-
ing sequences and most Alu elements
may be inserted into genomic sites that
do not complement their pol III promot-
ers. Furthermore, most Alu sequences are
heavily methylated at CpG positions that
are also present in the promoter region.
The methylation occurs at position 5 of cy-
tosine residues. Deamination of 5-methyl
cytosine produces thymine – a mutation
that is likely to escape the repair mech-
anism. As a result, CpG dinucleotides
mutate to TpG and CpA at a rate ap-
proximately ten times higher than that
of the non-CpG dinucleotides. Other re-
gions of rapid mutations include A-rich
linker and tail regions often associated
with microsatellite expansion. This rapid
rate of mutations represents another po-
tential way to eliminate or mitigate the
ability of any particular Alu repeat to mo-
bilize. Thus, the majority of Alu repeats
appear to be fossil relics that integrate
in the genome and accumulate mutations
in a random manner, characteristic of
pseudogenes.
The human Alu family has been di-
vided into nine major subfamilies: AluJo,
Jb, Sz, Sx, Sg, Sq, Sp, Sc, and Y, or-
dered approximately from the oldest to
the youngest (Table 2). AluJo and Jb form
a separate branch distinct from the AluS
branch that includes all the other seven
major subfamilies. Each Alu subfamily
represents a set of elements derived from
a small group of closely related master
genes. As a result, members of the same
family share, in principle, the same con-
sensus sequence, which is different from
Tab. 2
Average chromosomal density and estimated age of major Alu subfamilies.
Alu subfamily
a
AluJo
AluJb
AluSz
AluSx
AluSg
AluSq
AluSp
AluSc
AluY
Number
b
216 465
130 297
192 932
155 182
88 697
106 344
61 465
47 071
146 176
Proportion
c
18.91
11.3
16.9
13.6
7.8
9.3
5.4
4.1
12.8
Genomic density
(%)
1.60
1.1
1.9
1.5
0.9
1.0
0.6
0.5
1.4
Age (Myr)
d
81
81
48
37
31
44
37
35
19
a
Alu subfamilies were classiFed by censor. Alu classiFcation may slightly differ between different
programs and parameters used for Alu detection.
b
Numbers of Alu elements from major subfamilies present in the sequenced part of the human
genome (2805 Mb).
c
Proportions of elements from the corresponding subfamilies relative to all Alu sequences.
d
Age (in million years), based on Kimura’s distance.
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