Recovering signatures of archaic hominin introgression using ancestral recombination graphs
TL;DR
Imagine your family tree, but instead of just humans, some of your ancient ancestors had babies with other human-like creatures. Scientists already knew about two of these: Neanderthals and Denisovans. But this new computer tool called TRACE looked at the DNA of thousands of people alive today and found evidence of a THIRD mystery group — one we've never found bones or fossils from. It's like finding fingerprints in your house from a visitor you have no photos or records of. TRACE is clever because it doesn't need to have DNA from those ancient relatives to find their traces — it just looks at patterns in modern human DNA that are so old and unusual they must have come from somewhere else entirely. Even more surprising: this mystery DNA shows up in people from ALL over the world, including Africa, suggesting the interbreeding happened before humans even spread out across the globe.
Admixture between modern humans and extinct hominins has shaped the genomes of present-day individuals, but reconstructing this history has been constrained by the scarcity of archaic samples and unadmixed outgroup populations. We introduce TRACE, a reference- and outgroup-free approach that uses features of ancestral recombination graphs to identify archaic ancestry. Simulations show TRACE has high precision and low false discovery rates. Applied to 1000 Genomes, TRACE recovers known Neanderthal and Denisovan introgression and uncovers ghost admixture from uncharacterized hominins in both Africans and non-Africans. Ghost ancestry persists in Neanderthal and Denisovan ancestry deserts, challenging their interpretation as Homo sapiens-specific regions. In Oceanians, TRACE finds deep lineages are enriched in Denisovan compared to Neanderthal regions, supporting super-archaic introgression. TRACE enables mapping archaic introgression without archaic genomes.
- 1TRACE, a novel reference- and outgroup-free hidden Markov model method using ancestral recombination graphs, achieves high precision (~90%) and low false discovery rates (<0.25%) for detecting archaic introgression without requiring archaic reference genomes or unadmixed outgroup populations.
- 2TRACE identifies ghost archaic ancestry (0.5-1.1% per individual) from an unknown hominin lineage in all modern human populations studied, suggesting a pre-Out-of-Africa introgression event from a lineage that diverged approximately 0.83 million years ago.
- 3Ghost ancestry persists within previously defined Neanderthal and Denisovan ancestry deserts, suggesting these regions reflect lineage-specific selection against Neanderthal and Denisovan introgression rather than positive selection for Homo sapiens-specific variation.
- 4In Oceanian genomes, deeply diverged lineages are significantly enriched within Denisovan-introgressed segments compared to Neanderthal segments, supporting the presence of super-archaic introgression with coalescence times of approximately 1.77 million years ago.
- 5Ghost ancestry peaks are functionally enriched in immune and metabolic pathways including the major histocompatibility and lipoprotein complexes, while super-archaic segments in Oceanians show enrichment for MHC and activity-related cytoskeleton pathways.
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