If you think Europe’s royal families had a limited gene pool after centuries of inbreeding, consider the Neandertals of Siberia. In a report on the most complete genome of a Neandertal ever sequenced, an international team of researchers has found that the parents of a Neandertal woman from Siberia were as closely related as half-siblings.

The genome also shows that at some point the Neandertals interbred with other human groups, including their cousins the Denisovans, and our own modern human ancestors. There are even signs of Denisovans interbreeding with a mysterious archaic species. In all, the study suggests very close encounters among the several kinds of hominins living in the past 125,000 years. The detailed genome of the extinct Neandertals—our closest relatives—also offers a new look at the genetic differences that set our species apart from all the others.

The Neandertal DNA came from a toe bone, which dates to as old as 50,000 years ago, found in 2010 at the bottom of Denisova Cave in the Altai Mountains of Siberia. DNA from a finger bone from the cave revealed the identity of a new type of human in 2010—the Denisovans, who were close relatives of Neandertals. The cold cave preserved the DNA in both the Neandertal toe bone and Denisovan finger bone so well that a team led by Svante Pääbo, a paleogeneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, was able to produce high-quality genomes, in which each position of DNA was sequenced on average 50 times over. Although the group published a draft sequence patched together from different Neandertals in Europe in 2010, it was of much lower quality and had many gaps.

By comparing this Siberian Neandertal’s genome directly with the genetic codes of the Denisovan, another Neandertal from the Caucasus and 25 modern humans, Pääbo and his colleagues could tell that this Siberian Neandertal was the product of inbreeding and that her ancestors also chose their mates from their extended family. This suggests that this Neandertal woman came from a small, isolated population, the team reports online today in Nature. Researchers have known for several years that Neandertals in Europe had far less genetic diversity than modern humans alive at the same time. But “it was surprising that they were half-sibs or something like that,” Pääbo says.

The genome also revealed cases of interbreeding, in which Neandertals exchanged DNA with our species (Homo sapiens) and Denisovans. Today, living humans outside of Africa have inherited about 1.5% to 2% of their DNA from Neandertals, the paper suggests, matching previous estimates.

Not only did Neandertals, Denisovans, and modern humans interbreed, but the researchers have also detected DNA from an even more archaic human —perhaps Homo erectus—in the genome of Denisovans. “Interbreeding, albeit of low magnitude, occurred among many hominin groups,” the authors write in the new report. Co-author Montgomery Slatkin, a population geneticist at the University of California, Berkeley, explains that “the rate of interbreeding, meaning the fraction of genes exchanged between populations is typically small, 1-5% or so.”

Given repeated incidents of interbreeding but only small amounts of archaic DNA getting passed on to future generations, it seems that different groups of archaic humans mixed it up with each other whenever they could, but that these encounters were rare. Or, it is possible that biological or cultural barriers prevented the offspring from surviving, Pääbo says.

Now that Pääbo and his colleagues have high-quality copies of Neandertal and Denisovan DNA, they also are compiling a genome-wide catalog of DNA that is unique to Homo sapiens—sites where present-day people differ from Neandertals and Denisovans. So far, they have identified unique sequences of DNA involved in the development of neurons in the neocortex of the human brain, including early in fetal development, although they can’t yet say what each gene does. “Now we can go after these differences and study them,” Pääbo says. “The catalog is really pointing to the future.”

Other researchers note that this high-quality Neandertal genome is the culmination of a project that was considered bold when Pääbo launched it in 2006. “The correct sequencing of Neandertal DNA is an important achievement,” says geneticist Tomas Lindahl of London Research Institute. “The most remarkable achievement … has been to show that genetically meaningful and credible sequence data can be obtained from these fossil[s].” He is particularly interested in finding genes that modern humans have inherited from Neandertals that either cause disease or protect us from it.

There is now “evidence of mixture with even more ancient lineages,” notes paleoanthropologist Milford Wolpoff of the University of Michigan, Ann Arbor, who has long championed the idea of such mixture throughout human evolution. “These are exciting times for prehistorians.”