Selective enrichment of damaged DNA molecules for ancient genome sequencing

  1. Matthias Meyer
  1. Max Planck Institute for Evolutionary Anthropology, Evolutionary Genetics Department, Deutscher Platz 6, D-04103 Leipzig, Germany
  1. Corresponding authors: marie_gansauge{at}eva.mpg.de, mmeyer{at}eva.mpg.de

Abstract

Contamination by present-day human and microbial DNA is one of the major hindrances for large-scale genomic studies using ancient biological material. We describe a new molecular method, U selection, which exploits one of the most distinctive features of ancient DNA—the presence of deoxyuracils—for selective enrichment of endogenous DNA against a complex background of contamination during DNA library preparation. By applying the method to Neanderthal DNA extracts that are heavily contaminated with present-day human DNA, we show that the fraction of useful sequence information increases ∼10-fold and that the resulting sequences are more efficiently depleted of human contamination than when using purely computational approaches. Furthermore, we show that U selection can lead to a four- to fivefold increase in the proportion of endogenous DNA sequences relative to those of microbial contaminants in some samples. U selection may thus help to lower the costs for ancient genome sequencing of nonhuman samples also.

Footnotes

  • Received February 21, 2014.
  • Accepted June 16, 2014.

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