New molecular technique that enables the enrichment of uracil-containing DNA molecules during library preparation.

Contamination with 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 feature of ancient DNA, the presence of deoxyuracils, for selective enrichment of endogenous DNA against a complex background of contamination at the stage of DNA library preparation. By applying the method to Neanderthal DNA extracts that are heavily contaminated with present-day human DNA, we show that the amount of useful sequence information is increased approximately 10-fold and that the resulting sequences are more efficiently depleted of contaminants than by using purely computational approaches. Furthermore, we show that U selection can lead to a substantial increase in the proportion of endogenous DNA sequences relative to those of microbial contaminants.