| Summary: | This thesis addresses gaps that exist in the theory and knowledge of ancient DNA (aDNA). Much of the underlying basis of the field has been neglected in the excitement that followed the first aDNA studies. Therefore the results of many studies have been based on untested assumptions about the nature of post mortem DNA damage, sample preservation, contamination, and the efficacy of sample decontamination techniques. The validity of such results is questionable if the assumptions prove false. Hydrolytic post mortem DNA damage may modify recovered aDNA sequences. This thesis reports new insights into the biochemical basis of, predisposition of certain sequences and nucleotide positions towards, and subsequent effects of, such damage. Parallels of post mortem damage with in vivo mutation also enable insights into DNA sequence evolution. The long-term survival of DNA, and contamination of samples with exogenous DNA are two related problems characteristic to aDNA. The survival of endogenous DNA within bone, teeth and hair samples, the susceptibility of such samples to contamination, and the efficacy of decontamination techniques used to remedy such problems are investigated. The results highlight serious flaws in using bone and teeth as a DNA source. In contrast, the results demonstrate that hair may present a valuable DNA source for future studies. Numerous studies have reported the retrieval of ancient pathogen DNA from human samples. Analyses of the DNA content within teeth extracted from putative victims of the 2<sup>nd</sup> plague argue that such studies are at great risk from DNA degradation, and contamination arising due to environmental microorganisms. An extrapolation of these results using basic physical and chemical theory is used to evaluate the potential survival of aDNA in ancient Egyptian remains. This suggests that positive results from such samples are unlikely.
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