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Published online on August 21, 2007, 10.1073/pnas.0704665104
PNAS | September 11, 2007 | vol. 104 | no. 37 | 14616-14621


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BIOLOGICAL SCIENCES / BIOCHEMISTRY
Patterns of damage in genomic DNA sequences from a Neandertal

Adrian W. Briggs*,{dagger}, Udo Stenzel*, Philip L. F. Johnson{ddagger}, Richard E. Green*, Janet Kelso*, Kay Prüfer*, Matthias Meyer*, Johannes Krause*, Michael T. Ronan§, Michael Lachmann*, and Svante Pääbo*,{dagger}

*Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany; {ddagger}Biophysics Graduate Group, University of California, Berkeley, CA 94720; and §454 Life Sciences, Branford, CT 06405

Contributed by Svante Pääbo, May 25, 2007 (received for review April 25, 2007)

High-throughput direct sequencing techniques have recently opened the possibility to sequence genomes from Pleistocene organisms. Here we analyze DNA sequences determined from a Neandertal, a mammoth, and a cave bear. We show that purines are overrepresented at positions adjacent to the breaks in the ancient DNA, suggesting that depurination has contributed to its degradation. We furthermore show that substitutions resulting from miscoding cytosine residues are vastly overrepresented in the DNA sequences and drastically clustered in the ends of the molecules, whereas other substitutions are rare. We present a model where the observed substitution patterns are used to estimate the rate of deamination of cytosine residues in single- and double-stranded portions of the DNA, the length of single-stranded ends, and the frequency of nicks. The results suggest that reliable genome sequences can be obtained from Pleistocene organisms.

454 | deamination | depurination | paleogenomics

Author contributions: A.W.B., R.E.G., and S.P. designed research; J. Kelso, K.P., J. Krause, and M.T.R. contributed new reagents/analytic tools; A.W.B., U.S., P.L.F.J., R.E.G., M.M., M.L., and S.P. analyzed data; and A.W.B., P.L.F.J., R.E.G., and S.P. wrote the paper.

The authors declare no conflict of interest.

Data deposition: The sequences reported in this paper have been deposited as follows. Directly sequenced Neandertal and mammoth sequences have been deposited in the European Molecular Biology Laboratory database (Neandertal accession nos. CAAN02000001-CAAN02470991, mammoth accession nos. CAAM02000001–CAAM02064265) and in the National Center for Biotechnology Information trace archive under GenomeProject IDs 18313 (Neandertal) and 17621 (mammoth). Cave bear and contemporary human sequences have been deposited in the National Center for Biotechnology Information trace archive under GenomeProject IDs 19671 (cave bear) and 19675 (human).

This article contains supporting information online at www.pnas.org/cgi/content/full/0704665104/DC1.

{dagger}To whom correspondence should be addressed. E-mail: briggs{at}eva.mpg.de or paabo{at}eva.mpg.de

© 2007 by The National Academy of Sciences of the USA


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