Anthology of Human Repetitive DNA
261
protects chromosome ends from degrada-
tion, fusion, and recombination.
The length of telomeres appears to de-
pend on the number of cell divisions with
a general tendency toward shortening.
This has been implicated in chromoso-
mal aberrations, involving translocations
in differentiated and abnormal cells. The
length of telomeres has been used as a
measure of the age of individual cells and
is implicated indirectly in aging. It is still
unclear whether changes in the telomere
length have a direct impact on the aging
process of a cell or whether they are the
consequence of aging, possibly through a
decrease in the telomerase Fdelity.
The 100 to 300-kb long sequences ad-
jacent to telomeric repeats are called
subtelomeric repeats
.T
h
e
yr
e
p
r
e
s
e
n
tt
h
e
boundary between the telomere and the
rest of the chromosome. Most subtelom-
eric repeats contain motifs similar to
TTAGGG, but there are exceptions such
as
REP522
. Unlike telomeric repeats, most
subtelomeric repeats are not substantially
conserved in vertebrates. In fact, they
are highly polymorphic in humans and
even in different chromosomes. The distal
ends of human chromosomes are char-
acterized by an enhanced rate of recom-
bination and aberrations in subtelomeric
regions have been shown to be associated
with several congenital abnormalities. The
high divergence of subtelomeric repeats
may prevent recombinations between non-
homologous chromosomes and increase
their stability.
3
Interspersed Repeats
Usually, interspersed repeats are scattered
remnants of transposable elements that
were transpositionally active either in
the human genome or genomes of our
evolutionary ancestors. Active TEs have
produced families and subfamilies of
interspersed repeats of different age and
size. There are over 600 families of
human interspersed repeats represented
in Repbase (Sect. 6.1). Most of them
originated and became extinct during the
last 30 to 150 million years but some of
the oldest ones ceased to proliferate as
long as 200 million years ago and are
barely identiFable by sequence analysis.
Detectable interspersed repeats represent
45% of the human genome. Given the
limits of detectability, it is very likely that
the bulk of the remaining nonprotein
coding DNA is also composed of very old,
unrecognizable remnants of TEs.
The consensus sequence of a TE can
be reconstructed by applying the so-called
simple majority rule
to its multiply aligned
interspersed copies (±ig. 2). The average
similarity of diverged repeats to their
consensus sequence (
y
) is higher than
the average similarity between individual
repeats (
x
). The approximate relation
between the two variables is given by the
following simple formula:
y
=
1
+
12
x
3
4
.
In many cases, consensus sequence is a
quite accurate approximation of the orig-
inal TE that generated a particular family
of repeats. It can be further improved
by correcting stop codons in open read-
ing frames (OR±s) or restoring rapidly
mutating CpG dinucleotides, which some-
times erroneously converge to CpA or TpG
in the consensus sequence. At least one
TE reconstructed this way, named
Sleep-
ing Beauty
, has been shown to transpose
in vivo
.
Transposable elements harbored by the
human genome can be divided into three
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