RESEARCH ARTICLE · Science · 2010

Targeted Investigation of the Neandertal Genome by Array-Based Sequence Capture

Hernán A. Burbano, Emily C. Hodges, Richard Edward Green, Adrian W. Briggs, Johannes Krause, Matthias Meyer, Jeffrey Martin Good, Tomislav Maričić, Philip L. F. Johnson, Zhenyu Xuan, Michelle G. Rooks, Arindam Bhattacharjee, Leonardo Brizuela, Frank Wolfgang Albert, Marco de la Rasilla Vives, Javier Fortea, Antonio Rosas, Michael Lachmann, Gregory J. Hannon, Svante Pääbo

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Abstract

It is now possible to perform whole-genome shotgun sequencing as well as capture of specific genomic regions for extinct organisms. However, targeted resequencing of large parts of nuclear genomes has yet to be demonstrated for ancient DNA. Here we show that hybridization capture on microarrays can successfully recover more than a megabase of target regions from Neandertal DNA even in the presence of approximately 99.8% microbial DNA. Using this approach, we have sequenced approximately 14,000 protein-coding positions inferred to have changed on the human lineage since the last common ancestor shared with chimpanzees. By generating the sequence of one Neandertal and 50 present-day humans at these positions, we have identified 88 amino acid substitutions that have become fixed in humans since our divergence from the Neandertals.

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