558
Chimpanzee Genome
shared a common ancestor after the sepa-
ration of the gorilla lineage.
However, conclusions based on hy-
bridization experiments have been treated
with caution since
1
T
m
is likely to be
partially determined by factors of uncer-
tain identity. The unclear influence of
experimental conditions and of genomic
organization such as the presence of du-
plications, which facilitates hybridization
of nonhomologous DNA sequences, were
among the main points of critique.
1.2.2
Mitochondrial DNA
In the pre-PCR era, the use of nucleic acids
for phylogenetic analyses was substantially
complicated by the need to reproducibly
isolate the region of interest – usually a
fragment of a few hundred base pairs
(bp) – from a genome several million to
few billion base pairs in size. To minimize
this problem, initial focus was laid on
thegenomeo
fm
i
tochond
r
ia
,wh
ichha
s
a size of only approximately 16 000 bp in
humans, and is generally present in more
than 1000 copies per cell.
Isolated mitochondrial genomes from
the hominoid species have been compared
by two different methods. Restriction en-
zymes – enzymes that cut DNA at speciFc
recognition sites – can be used to test
for the presence and relative position of
their respective cleavage site in a DNA
sequence (the phylogenetic informative
character in this approach). On the basis
of restriction maps of their mitochondrial
genomes, chimpanzees were placed – in
contrast to results from other molecular
comparisons – closer to gorillas than to
humans. However, little statistical support
was provided for that conclusion and alter-
native phylogenies were almost as likely.
Similar to the situation with comparative
analyses of proteins, the most accurate way
to determine the exact degree of difference
between nucleic acids is to directly com-
pare their sequences. Parts, and later,
the sequences of the entire mitochondrial
genome of hominoids were determined
and compared. In these studies, chim-
panzees appear again to be closer related
to humans than to gorillas.
1.2.3
Nuclear DNA
Meanwhile, modern techniques of molec-
ular biology provide a rapid and repro-
ducible access to the DNA sequence of
almost any region in a genome. As a
consequence, a variety of data sets have
been collected from the nuclear genome
that address the question of hominoid
phylogeny with particular regard to the re-
lationship of humans, chimpanzees, and
gorillas (Table 1). ±or practical reasons,
early studies compared DNA sequences
of coding regions from genes. Later, in-
creasing focus was laid on the comparison
of noncoding and potentially nonfunc-
tional DNA sequences such as introns,
pseudogenes, or intergenic regions. These
DNA sequences appear to be the best
possible data source for phylogenetic stud-
ies on closely related species. However,
as can be clearly seen in Table 1, the
supported phylogenetic relationship of hu-
mans, chimpanzees, and gorillas varies
according to the analyzed genomic region.
Apparently, two factors have prevented
the hominoid phylogeny from being de-
termined by means of molecular com-
parisons: Frst, the insufFcient accuracy
and resolution of most comparative meth-
ods, and second, ambiguous information
content in the molecular data itself. In
order to determine which of the alter-
native phylogenies represents the true
order in which the lineages to the indi-
vidual hominoid species emerged (species
tree), it is necessary to understand why
phylogenetic trees estimated from DNA
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