Chimpanzee Genome
563
eight additional chromosomes in humans.
The reason for these rapid changes in the
subtelomeric region of chromosomes is
still unclear.
From the analysis of the human genome
draft sequence, it emerged that about 5% of
the DNA sequence – preferentially in the
regions around the centromeres – repres-
ents evolutionary recent duplications of
chromosomal segments with a DNA se-
quence identity of
>
90%. Interestingly,
initial calculations reveal that more than
7000 exons are transcribed from these
duplicated segments. Thus, gene dupli-
cations due to segmental duplications pro-
vide good candidates for species-speci±c
evolution. Comparing the duplication pat-
tern for human chromosome 22 between
humans and chimpanzees, differences are
seen, which imply that loss and gain of du-
plicated elements is an ongoing process in
human and chimpanzee evolution. How-
ever, comparative analyses focusing on
segmental duplications have just started.
Therefore, the exact amount of differen-
tially duplicated segments in the chim-
panzee and human genomes as well as the
number and identity of possibly involved
genes remains to be determined.
Around 45% of the human genome
consists of repetitive DNA sequences due
to the expansion of various groups of
mobile elements in the genome. As an
example, a particular class of repeats
termed
Alu-elements
are present in more
than one million copies in the human
genome comprising
10% of the entire
DNA sequence. Even though the overall
mobility of transposable elements has
markedly decreased over the past 35
to 50 million years, transposition is still
ongoing in the human and, presumably,
also in the chimpanzee genome.
Repetitive elements can propagate ge-
netic
differences
between
species
by
mainly two ways. First, the insertion of
individual transposable elements into reg-
ulatory or coding regions of genes can alter
expression and function of the affected
genes. As an example, humans differ
from chimpanzees – and from all other
primates – by an inactivation of a gene
CMAH
whose product is essential for the
generation of a certain glycoprotein. This
inactivation is due to a human-speci±c in-
sertion of an Alu-element that replaced a
92-bp long exon and, in addition, causes
a frameshift in the subsequent coding
sequence. The gene modi±ed thus is ex-
pressed into a truncated and nonfunctional
protein and is responsible for the only
proven biochemical difference between
chimpanzee and human cells to date.
Second, intrachromosomal crossing-over
mediated by direct or inverted repetitive
elements can cause deletions and inver-
sions, respectively. For example, exon 35
of the human tropoelastin gene has been
deleted presumably by a recombination
event between two flanking Alu-elements.
In summary, several factors can account
for genetic differences between humans
and chimpanzees on a subchromosomal
scale. However, a determination of the ex-
tent to which they each contribute to the
total amount of differences between both
genomes must await more comprehen-
sive studies.
2.3
Substitutional DNA Sequence Differences
The most frequently detected difference
between chimpanzee and human DNA
sequences is caused by substitutions of
individual nucleotides. Initial studies sug-
gested that per 200 compared nucleotide
positions, only about 3 differ between
humans and chimpanzees, equivalent to
a mean sequence difference of around
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