Chimpanzee Genome
575
However, there is one important issue
when working with this draft sequence
that played only a very minor role in
previous comparative studies of genome
sequences. Errors in the draft sequence
of the chimpanzee genome, but also
in the human genome sequence due
to errors in the assembly process or
due to sequencing errors suddenly gain
relevance. An attempt to identify conserved
regions between distantly related species
is conservative with respect to the quality
of the draft sequence. Regions that have
been found conserved between species
using early versions of the draft sequence
have a high probability of remaining
conserved after sequencing errors in the
draft sequence have been corrected. It is
self-evident that the situation is certainly
more difFcult when the focus lays on DNA
sequence differences between genomes as
in the case of the human–chimpanzee
comparison. To minimize this problem,
every DNA sequence position in the draft
version of the chimpanzee genome should
get assigned a conFdence value to allow a
quick assessment of its reliability.
5.3
Human, Chimpanzee, and
...
Future
Perspectives
With the availability of the chimpanzee
genome draft sequence, the Frst step into
the next stage of comparative genomics
will be completed. A comprehensive cata-
log of genetic differences between humans
and chimpanzees will emerge that ulti-
mately reveals those changes responsible
for the distinct phenotypic traits of both
species. The identiFcation of those pre-
sumably few functional changes and the
dating of their presumed occurrence will
be the main task of future studies. To ac-
complish this goal, it will be necessary to
exactly determine the extent and pattern
of genetic variation both within humans
and within chimpanzees. This not only
helps in identifying those genuine ge-
netic differences between both species that
cannot be attributed to polymorphisms
in either species but also helps pinpoint
those regions in the genomes of chim-
panzees and humans for which fewer than
average sequence variants exist. Such a
reduction of diversity can comprise signa-
tures of selection during recent human and
chimpanzee evolution and provide hints
for the likely importance of changes that
are close by in functional regions of the
genome.
Eventually, the detection of genuine ge-
netic differences between humans and
chimpanzees can only then be inter-
preted in a meaningful way when the lin-
eage on which the corresponding change
occurred has been determined. There-
fore, the genome of a third, more dis-
tantly related species is required as an
outgroup that helps infer whether an
observed DNA sequence difference be-
tween humans and chimpanzees is due
to
a
change
on
the
human
or
the
chimpanzee lineage. Presumably, a sec-
ond anthropoid primate would be op-
timal as such an outgroup. In order
to make full use of the genomic com-
parison of humans and chimpanzees,
the genome sequence of the outgroup
species should be determined immediately
following the completion of the chim-
panzee genome sequence. Likely candidate
species are two Old World monkeys reg-
ularly used in biomedical research: the
rhesus macaque (
Macaca mulatta
), and
the baboon (
Papio hamadryas
), or the
orangutan (
P
.
pygmaeus
). Which of these
species to choose depends largely on fu-
ture plans to use primates as experimental
animals.
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