Ancient DNA: From Molecules To Genomes

Traces of DNA molecules can survive up to hundreds of thousands of years in a wide range of fossils, such a bones, teeth, hairs, coprolithes and even in the soil. These molecules literally catch evolution red-handed, providing precious sources of information about past populations and communities, ancient epidemics and extinct species. Such templates, however, have been extensively damaged over time and present specific biochemical features, including hydrolytic degradation of nucleotidic bases, extensive fragmentation and oxidation marks. In addition, ancient DNA extracts most often consist of a mixture of DNA from different sources, as fossils are colonized by environmental microbes after death. These features have long limited our ability to access ancient DNA molecules and therefore have restricted the amount of genetic information that one could resurrect from the past. Over the last couple of years, the advent of next-generation sequencing has considerably changed this situation and unlocked access to the first complete genomes from the past. Brute-force sequencing of ancient genomes, however, is most often not cost-effective due to the metagenomic nature of ancient extracts. We will present how second and third-generation sequencing technologies can be used to illuminate the biochemical structure of ancient DNA molecules and, in turn, how specific molecular tools and bioinformatic approaches can be applied in order to improve our ability to deep-sequence and identify even traces of ancient DNA.