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http://www.2think.org/neanderthal.shtml
30 March 2000
Nature 404, 453 - 454 (2000) � Macmillan Publishers Ltd.
Ancient DNA: Neanderthal population genetics
MATTHIAS H�SS
Matthias H�ss is at the Swiss Institute for Experimental Cancer Research, Chemin des
Boveresses 155, 1066 Epalinges, Switzerland.
e-mail: Matthias.Hoss@isrec.unil.ch
Authenticity is all in research on ancient DNA. Experience has taught us that even the
most exciting claims of the retrieval of ancient DNA are not worth much if they cannot be
independently reproduced. Hence the importance of a paper on page 490 of this issue, in
which Ovchinnikov et al.1 describe the extraction, amplification and sequencing of DNA
from 29,000-year-old archaeological bone material of a Neanderthal recovered from the
Mezmaiskaya Cave in the northern Caucasus. This is the second time that such a claim has
been made, the first being in 1997 (ref. 2). The paper by Ovchinnikov et al. is probably
the more important of the two, for it provides invaluable corroboration for the
authenticity of Neanderthal DNA sequences. Moreover, sequences of the DNA from a second
Neanderthal offer more detailed insight into the contentious evolutionary relationship
between Neanderthals and modern humans.
Research into ancient DNA enjoys high publicity. It is perhaps the combination of modern
molecular techniques and 'old-fashioned' archaeology that catches the interest of the
scientific community and general public alike. This fascination sometimes clouds critical
judgement. But this area of research, like all others, must meet with standards that
ensure the authenticity and reproducibility of any given result. This has not always been
so. Several of the most spectacular claims — such as the retrieval of DNA sequences
from 15-million-year-old plant compression fossils3, from 80-million-year-old bones of
putative dinosaur origin4 and from insects of up to 130 million years in age trapped in
amber5-7 — could not be reproduced in any other than the original laboratories, and
so are of limited value8-11.
The relationship between Neanderthals and humans remains enigmatic, so the retrieval of
Neanderthal DNA has been one of the major goals of researchers in the field of ancient
DNA. The age of later Neanderthal populations is well within the range compatible with
reliable retrieval of ancient DNA (such retrieval is possible from samples up to 100,000
years old). However, it appeared from several studies (for example, ref. 12) that the work
done with ancient human remains was close to the technological limit of what is possible.
This is mainly because of the difficulty of distinguishing target sequences from
contaminating modern, in this case human, DNA.
So it came as no surprise that the publication of the first successful retrieval of DNA
from a Neanderthal, from the Feldhofer Cave in Germany2, was greeted with caution.
Although the paper was widely regarded as being of technically high quality, the remote
possibility remained that the published sequence was an artefact or the result of
contamination. The need for DNA sequences from a second, unrelated Neanderthal specimen
was clear, as echoed in most reviews of that paper. And this is where the importance of
the work of Ovchinnikov et al.1 lies.
Ovchinnikov and colleagues sequenced Neanderthal mitochondrial DNA and found that it is
closely related, but not identical, to that described previously. Like the first paper2,
the study of Ovchinnikov et al. is convincing in itself. The authors used all the
state-of-the-art controls to monitor artefacts and contamination, including having the
sequences verified by another laboratory. However, only the combination of the papers
allows us to appreciate fully their individual worth. The identification of two
Neanderthal DNA sequences, from different specimens found in locations far apart, that are
closely related but not identical, rules out the possibility that either sequence is an
artefact or the product of contamination. By verifying each other, the two papers provide
the most reliable proof so far of the authenticity of ancient DNA sequences.
Can we learn anything from this new Neanderthal DNA sequence about the relationship
between modern humans and Neanderthals? The new sequence shares with the Feldhofer one the
same surprising feature: it is no more closely related to DNA from modern European
populations than to sequences from any other modern human population. This argues against
the idea that modern Europeans are at least partly of Neanderthal origin. Although the two
sequences were taken from specimens at geographically distant locations, the number of
differences between the sequences indicates that these two individuals were from a single
gene pool. Furthermore, the variation between the two Neanderthal sequences is similar to
that among modern humans.
Details of the Mezmaiskaya sequence also support the suggestion2 that there was no
contribution of the Neanderthals to the pool of mitochondrial genes in modern human
populations. However, this does not exclude the possibility of a contribution of nuclear
Neanderthal genes. Approximate quantification of the number of mitochondrial DNA molecules
found in the Feldhofer Neanderthal ruled out any hope of recovering nuclear DNA from this
specimen2, but the apparently excellently preserved Mezmaiskaya specimen might yield
values compatible with retrieval of nuclear DNA.
Having achieved DNA sequencing from members of geographically distant Neanderthal
populations, it would be interesting to do the same for populations that are far apart on
the timescale. A specimen dated closer to the upper time limit of Neanderthal distribution
(about 230,000 years ago) would be a tempting choice for DNA retrieval.
The quality of the molecular data retrieved so far from Neanderthal specimens is
compelling. If this is how research on ancient DNA is going to proceed, then we are truly
on our way to Neanderthal population genetics.
References
1. Ovchinnikov, I. V. et al. Nature 404, 490-493 (2000).
2. Krings, M. et al. Cell 90, 19-30 (1997).
3. Golenberg, E. M. et al. Nature 344, 656-658 (1990).
4. Woodward, S. R., Weyand, N. J. & Bunnell, M. Science 266, 1229-1232 (1994).
5. DeSalle, R., Gatesy, J., Wheeler, W. & Grimaldi, D. Science 257, 1933-1936 (1992).
6. Cano, R. J., Poinar, H. N., Roubik, D. W. & Poinar, G. O. J. Med. Sci. Res. 20,
619-622 (1992).
7. Cano, R. J., Poinar, H. N., Pieniazek, N. J., Acra, A. & Poinar, G. O. Jr Nature
363, 536-538 (1993).
8. Sidow, A., Wilson, A. C. & Pbo, S. Phil. Trans. R. Soc. Lond. B 333, 429-432
(1991).
9. Zischler, H. et al. Science 268, 1192-1193 (1995).
10. Austin, J. J., Ross, A. J., Smith, A. B., Fortey, R. A. & Thomas, R. H. Proc. R.
Soc. Lond. B 264, 467-474 (1997).
11. Walden, K. K. & Robertson, H. M. Mol. Biol. Evol. 14, 1075-1077 (1997).
12. Handt, O. et al. Science 264, 1775-1778 (1994).
Nature � Macmillan Publishers Ltd 2000 Registered No. 785998 England.
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