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Comparative genomics
of higher primates
including humans and neandertals
A
As more details emerge from
the genomes of humans1,2, our
closest living relatives the
apes3,4 and our closest extinct
relative the Neandertal, it will
become possible to say what defines us as a
species from a genetic point of view. Detailed studies of genes that carry humanspecific evolutionary traits should reveal
which ones have been especially important
during human evolution. Ultimately, these
efforts could uncover the biology beneath
human cognition, language and culture,
and might improve our understanding of
conditions such as autism, schizophrenia
and language impairments.
Ape ANcestry
The common chimpanzee and the bonobo
or pygmy chimpanzee are our closest living
relatives, with whom we share a common
ancestor that lived 5–7 million years ago.
Humans and chimpanzees share a common
ancestor with gorillas — the other major species of African apes — that lived 6–8 million
years ago, whereas the common ancestor
shared with the Asian orangutans lived
12–16 million years ago (Fig. 1).
Many species that were more closelyrelated to humans have lived and become
extinct since the time of the chimpanzeehuman ancestor. They are collectively called
hominins. One hominin is the Neandertal,
whose lineage diverged from ours 300,000–
500,000 years ago. Neandertals lived in
western Eurasia, sometimes alongside our
ancestors, until they became extinct around
30,000 years ago.
stAte of the Art
Our technical ability to sequence genomes is improving rapidly and the cost is
continually dropping. Soon it will be
possible to sequence mammalian genomes
accurately and cheaply in a matter of days.
At the same time, technologies that allow
high-speed surveys of proteomes and
metabolomes — that is, all the proteins and
metabolic molecules present in a tissue or
cell — are also being developed.
Today, the most complete primate genome
available is that of the
human; the genomes of
the chimpanzee, gorilla,
orangutan and rhesus
macaque are of lower
and variable quality.
This year, a group
of researchers published
the first draft of the
complete Neandertal genome5. Studying these
genomes will help researchers identify the
millions of nucleotide
changes, and tens of
thousands of insertions,
deletions and duplications of short stretches
of DNA, that have occurred since the
divergence of modern humans from
chimpanzees and, more recently, from the
Neandertals.
Next steps
Accurate comparative studies of the human
genome with those of other primates will
require genomic data of similar, high quality
for the living apes and extinct hominins.
However, the available ape genomes are
currently of low quality. Over the next few
years, researchers aim to sequence the
genomes of most monkey species and raise
ape genomes to human-level reliability.
A
first draft version of the Neandertal genome has recently
been produced at the Max planck Institute for evolutionary
Anthropology. It allows us to identify genomic features by
which all present-day humans differ from our closest evolutionary
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Research Perspectives of the Max Planck Society | 2010+
Also of great importance is variation
within species, as patterns of differences
in DNA sequence among individuals
allow identification of positive selection.
Several large projects (for example, HapMap,
ENCODE and 1000 Genomes) are providing insight into genomic variation
among humans, but there are no equivalent projects for ape or
primate genomes.
A simple first step
towards this type of undertaking would be to
collect blood and tissue
samples from captive
apes. These represent
only a limited sample of
the total ape genetic
variation; wild ape genetic samples are urgently needed, as these
populations are endangered and might disappear in coming decades.
Non-invasive samples,
such as faeces or hair,
from all great apes
across their entire current ranges should be collected and preserved for the future. Establishing ape cell
lines and sequence libraries from such
samples will extend their useful life.
More accurate Neandertal genome sequencing is also in progress, and should be
extended to several Neandertal individuals
and other extinct hominins. Researchers
should develop standards and protocols for
working with ancient DNA, particularly
ancient hominid DNA, to ensure that
results are reliable and not the product of,
for example, contamination of modern
human DNA.
However, it is not enough to compare
only DNA sequences within and between
relatives, as well as genomic regions that were subject to positive
selection during the evolution of fully modern humans (Green, R. E. et
al. Science, in the press).
Biology and Medicine
Better technology is allowing more ambitious genomic sequencing.
comparing our genome to those of both our closest living, and extinct,
relatives will reveal genes that are necessary for specific human traits.
understanding what makes us different from other species might help us
tackle human-specific diseases.
Diagram bonobo: Friends of Bonobos/ Photograph of skeleton courtesy of K. Mowbray. Reconstruction by G. Sawyer and B. Maley, copyright I. Tattersall
Fig. 1 | Tree of humans and apes
species; gene activity is also of crucial importance. Transcription patterns, splicing
variants and levels of gene expression in
different tissues need to be studied6.
Current efforts to study gene activity in
non-human primate genomes rely on the
assumption that gene structure, splicing
and regulatory RNA are largely similar to
those in humans.
Improved sequencing techniques will
allow RNA from each species to be studied
directly and will also help reveal the
activity of less well-studied portions of the
genome, such as those that do not encode
proteins. Together with mass spectroscopybased methods to study the proteome, this
will help scientists understand how the
genome relates to protein production —
in each cell and organ, and during the
course of an individual’s life.
4 - 6 million
years ago
6 - 8 million
years ago
12 - 16 million
years ago
prospect of prIMAte
evolutIoNAry geNoMIcs
Ultimately, analyses of extant and extinct
primate genomes coupled with the study
of gene activity in extant primates will
identify those DNA sequences that make
humans unique. To test the effects of these
sequences, it will be necessary to develop
novel in vitro experimental systems. One
such system could include tissue cultures
that mimic human tissues formed, for example, by the use of induced pluripotent
stem cells. Another approach could be
‘humanizing’ genes or whole pathways in
animal models such as the laboratory
mouse7. Genetic manipulations of such systems will then provide an avenue for testing aspects of traits specific to humans.
Understanding the biological basis for
human-specific characteristics such as
cognition, language and culture will be of
interest to society. It might also be of
medical utility in the case of conditions
such as speech disorders, autism and
schizophrenia that affect human-specific
traits. Better understanding of the genetic
roots of these abilities might help improve
treatments.
➟ For references see pages 38 and 39
Reproduced from ref. 8.
left
Skeletons of a Neandertal (left) and a human.
below
Artistic view of murine model systems.
2010+ | Research Perspectives of the Max Planck Society
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