The DNA molecule is a polymer composed of 2′ deoxyribose sugar units linked to each other via phosphate ester links (see figure below). To every sugar, a purine (adenine or guanine) or a pyrimidine (cytosine or thymine) is attached at the 1′ position by a glycosidic bond. In vivo, the DNA molecule is supported by water molecules in the major grooves, thus the molecule is never really dry. In addition nuclear DNA (not mitochondrial DNA) is wound tightly around histone proteins, which presumably absorb some of the surrounding damage. Despite this the DNA molecule is labile and prone to many forms of damage, all of which presumably limit the molecules “half-life” in the geosphere.

Unfortunately for the paleo-geneticist, comparatively speaking, the DNA molecule is one of the least stable molecules within our cells. It is the subject of rapid hydrolysis and oxidation over short time periods limiting its “life” in vivo and within the environment.

Once an organism dies, presumably the single most important factor in the long-term preservation of its DNA is the rate at which specific cellular enzymes, called nucleases, can be stopped. These endonucleases are efficient and can rapidly cleave DNA into small fragments. However as these are energy requiring functions, and a cell without oxygen will deplete its energy sources quickly, nuclease degradation may cease relatively soon post mortem. The organism must then face the bacterial, fungal and insect onslaught which can be quite effective but often incomplete. Once bacterial onslaught has slowed, the DNA molecule is still subject to chemical degradation via hydrolysis and oxidation. To understand the processes which degrade the DNA molecule in the fossil record and under what conditions these reactions are minimized, one needs to look briefly at the molecule itself and its susceptible sites.

The removal of the ribose sugars 2′ OH group, creating the deoxy-ribose sugar does afford the bonds joining two nucleotides (phosphodiester bond) increased strength, however it weakens the glycosidic bond joining the bases to the sugars. Diesters, like the bonds in the phosphate sugar backbone, are normally quite labile and subject to quick hydrolytic cleavage. It has been estimated that direct cleavage of the phosphate backbone is probably the most frequent type of hydrolytic damage the DNA molecule must cope with, generating single stranded nicks. In vivo, in a fully hydrated system this event takes place about once every 2.5 hours. It has been estimated that under dry conditions this rate drops some 20 fold.

Even when the remains of an organism “dry” (although there is nothing in nature that is 100% dry) the molecular components of a cell are still susceptible to oxidative attack. Free radicals such as peroxide radicals (.O2), hydrogen peroxide (H2O2), and hydroxy radicals (.OH) are all endogenously occurring products and hence are an important source of endogenous DNA damage, and are likely to play an important role in limiting the life of DNA in the fossil record. They may also derive from exogenous sources such as ionizing radiation, UV light and cellular processes during bacterial and fungal degradation. Recently DNA extractions from fossil remains were subject to gas chromotagrahpy mass spectrometry in the attempt to identify oxidative base damage. From all samples where no endogenous DNA could be retrieved higher levels of two oxidative forms of base damage, 5-Hydroxyhydantoin and 5-Hydroxy-5-methylhydantoin were detected. As these and many other oxidative lesions block the polymerase in PCR, and hence its ability to make copies, oxidative damage will also limit the successful retrieval of DNA from fossil remains.