Statistical Evidence for Miscoding Lesions in Ancient DNA Templates

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Abstract
It is generally believed that sequence heterogeneity in PCR products from fossil remains are due to regular DNA polymerase errors as well as miscoding lesions compounded by damage in the template DNA (Pääbo 1990 ; Handt et al. 1994b, 1996 ; Höss et al. 1996 ; Krings et al. 1997 ). However, it has been difficult to test the frequency with which this assumption holds. First, DNA extractions from fossil remains rarely produce a yield large enough for pre-PCR analysis of postmortem modifications (Höss et al. 1996 ). Second, in most cases, it is not possible to determine whether nucleotide misincorporations by the DNA polymerase enzyme during amplification are caused by regular DNA polymerase errors or miscoding lesions in the template DNA sequences (Greenwood et al. 1999 ). Finally, the error rates of the DNA polymerase enzymes for PCR have proved to be highly unpredictable, making it difficult to account for regular DNA polymerase errors in amplified DNA sequences (Eckert and Kunkel 1991 ).