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Science 17 November 2006:
Vol. 314. no. 5802, pp. 1113 - 1118
DOI: 10.1126/science.1131412
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Research Articles

Sequencing and Analysis of Neanderthal Genomic DNA

James P. Noonan,1,2 Graham Coop,3 Sridhar Kudaravalli,3 Doug Smith,1 Johannes Krause,4 Joe Alessi,1 Feng Chen,1 Darren Platt,1 Svante Pääbo,4 Jonathan K. Pritchard,3 Edward M. Rubin1,2*

Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where the human genomic sequence is different. These results enabled us to calculate the human-Neanderthal divergence time based on multiple randomly distributed autosomal loci. Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent common ancestor ~706,000 years ago, and that the human and Neanderthal ancestral populations split ~370,000 years ago, before the emergence of anatomically modern humans. Our finding that the Neanderthal and human genomes are at least 99.5% identical led us to develop and successfully implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics.

1 U.S. Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA.
2 Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.
3 Department of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
4 Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103, Leipzig, Germany.

* To whom correspondence should be addressed. E-mail: emrubin{at}lbl.gov

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