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      Patterns of damage in genomic DNA sequences from a Neandertal.

      Proceedings of the National Academy of Sciences of the United States of America
      Bacteriophage T4, enzymology, Base Sequence, Computer Simulation, Cytosine, metabolism, DNA, genetics, history, DNA Damage, DNA-Directed DNA Polymerase, Deamination, Genome, Genomic Library, History, Ancient, Humans, Likelihood Functions, Models, Biological, Molecular Sequence Data, Paleontology, methods, Polymerase Chain Reaction, Reference Standards, Sequence Analysis, DNA, Templates, Genetic

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          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.

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