Ancient DNA (aDNA) sequencing is like unlocking a genetic time capsule, almost bringing the past back to life and offering direct insights into the evolutionary processes that have shaped the living world. Yet, accessing DNA from ancient remains is still far from guaranteed, and the meticulous ‘tour de force’ required to retrieve aDNA molecules is often overlooked. A prime example illustrating both the promise and challenging effort behind aDNA research is the mid-Ice Age Sima de los Huesos hominin sequencing project by Matthias Meyer and his collaborators. As the oldest human for whom genomic data have been successfully retrieved, the Sima de los Huesos specimen not only offers a window into ancient human history but also demonstrates scientific genius in action and marks a triumph of modern technology, underscoring how far aDNA studies have come and the challenges that remain.

Consequently, the team generated new data from libraries enriched with Denisovan-specific mtDNA probes but recovered human aDNA in only a quarter of them, with high levels of present-day human contamination. By focusing on DNA sequences under 45 bases in length, bearing characteristic aDNA damage patterns, the researchers reconstructed 98% of this individual’s mitochondrial genome, confirming the surprisingly closer connection between the Sima de los Huesos mtDNA lineage and Denisovans and shedding new light on the complex evolutionary landscape of the mid-Ice Age.