Like a ghost

To test the tool, they had convenient examples: the Neanderthal and Denisovan sequences we’ve already identified in the human genome. If TRACE couldn’t pick those out, it wouldn’t find anything else useful. The development of ancestral recombination graphs is still a work in progress, so the researchers used two different tools to generate them and stuck with the one that produced the best results. The combination produced a very low false discovery rate (less than a quarter of a percent) while having an accuracy of over 90 percent.

In another demonstration, the researchers performed the analysis on African populations, which only received Neanderthal and Denisovan DNA when individuals from Eurasia migrated back. TRACE found only 0.1 percent of ancestry from these archaic lineages in these African genomes, consistent with its low false error rate.

Given about 500 modern human genomes, TRACE pulled out the expected Neanderthal and Denisovan segments. But it also revealed a lot of DNA from a ghost lineage. The percentage was small, at about 0.5 to 1.1 percent of current human genomes. But collectively, they covered nearly 1.5 billion bases. For context, the full human genome is three billion bases.

It was present in all modern human populations, indicating that the interbreeding occurred before the out-of-Africa expansion. But African populations carry more diverse segments and some that are distinct, a consequence of some of the diversity that was lost when only a fraction of the total population expanded into Eurasia. In fact, the researchers could identify about 100 areas of the genome that lack ghost lineage DNA entirely in non-African populations.

Based on the last common ancestor of the sequences, the researchers estimate that the lineage last shared a common ancestor with modern humans over 800,000 years ago, making it about the same age as the split with the ancestor of Neanderthals and Denisovans. The segments in the human genome are, on average, shorter than Neanderthal and Denisovan segments. This means they’ve been around in the modern human genome longer, which is consistent with them having arrived before modern humans left Africa.