Extracting this degraded DNA requires careful procedure. Researchers take a small sample from the interior of the bone, where degradation tends to be slower than on the surface. They grind the sample, dissolve it in a chemical solution designed to free the DNA from the surrounding matrix, and then use a series of purification steps to concentrate the genetic material and remove contaminants. The resulting extract typically contains far more microbial and environmental DNA than hominin DNA—in many ancient samples, the fraction of DNA that actually came from the individual is a small percentage of the total.
From this concentrate, researchers build a sequencing library: a collection of short DNA fragments that can be read by a sequencing machine. Because the fragments are so short and so damaged, the sequencing must be done at high coverage—meaning the genome must be read many times over, with different starting points, so that the overlapping reads can be assembled into a coherent whole. Errors and damage patterns that appear on individual reads can be identified and corrected when the same region has been read dozens or hundreds of times.
Contamination is the persistent concern of the field. A researcher’s own DNA, bacteria that entered the bone after burial, and modern environmental contamination can all appear in an ancient DNA extract. The laboratory procedures required to minimize this are stringent: work in positive-pressure clean rooms where airflow is carefully controlled, use of protective equipment, frequent surface decontamination, and statistical methods for distinguishing genuine ancient DNA from contaminants. The Max Planck Institute for Evolutionary Anthropology, where the Denisova Cave genomes were sequenced, maintains dedicated ancient DNA facilities precisely because of these demands.