UC Berkeley researchers have developed a new computational technique that identifies regions of the human genome inherited from previously unknown archaic hominins, using only genome sequences from present-day humans. The method, called TRACE (TRacking Archaic Contributions via ARG Estimation), reconstructs an ancestral recombination graph (ARG)—a detailed map of how DNA segments across the genome are related through shared ancestry over time—from hundreds of modern human genomes.
While ancient DNA extracted from Neanderthal and Denisovan fossils previously revealed those lineages’ contributions to the modern human genome, no DNA has been recovered from other extinct hominins, making their contributions difficult to detect. TRACE addresses this by identifying genomic regions whose ancestry traces back unusually far in time, even without a reference ancient genome.
“Genealogies preserve a record of our evolutionary past,” said Priya Moorjani, senior author of the paper published in Science. “TRACE reconstructs those histories across the genome. By identifying regions whose ancestry extends unusually far back in time, we can uncover genetic contributions from extinct human populations, even in the absence of ancient DNA.”
Applying TRACE to modern genome data, the team confirmed known regions of Neanderthal DNA, which makes up about 1% of the human genome, and correctly identified Denisovan introgression in genomes from Asia and Oceania. But many ancient regions matched neither lineage. The researchers traced these segments to two distinct, previously uncharacterized lineages with different introgression timelines: a “ghost” lineage found in all modern human genomes, comprising roughly 0.5% to 1% of each individual’s genome, and a “super-archaic” lineage detected only in regions of Denisovan ancestry within genomes from Oceania, where Denisovan DNA reaches up to 4%.
“We discovered that about 2% of the modern human genome is from archaic hominins,” said Yulin Zhang, co-first author of the study. Arjun Biddanda, co-first author, noted that “These contributions are widespread throughout the genome, and ghost ancestry is detected even in regions previously thought to be intolerant of Neanderthal and Denisovan ancestry.”
Many of these archaic segments are enriched in genomic regions associated with immunity and metabolic function. Moorjani said she hopes expanding genome databases and additional Denisovan genome sequences will help detect further archaic lineages, adding that TRACE “should also work with other species.”
While ancient DNA extracted from Neanderthal and Denisovan fossils previously revealed those lineages’ contributions to the modern human genome, no DNA has been recovered from other extinct hominins, making their contributions difficult to detect. TRACE addresses this by identifying genomic regions whose ancestry traces back unusually far in time, even without a reference ancient genome.
“Genealogies preserve a record of our evolutionary past,” said Priya Moorjani, senior author of the paper published in Science. “TRACE reconstructs those histories across the genome. By identifying regions whose ancestry extends unusually far back in time, we can uncover genetic contributions from extinct human populations, even in the absence of ancient DNA.”
Applying TRACE to modern genome data, the team confirmed known regions of Neanderthal DNA, which makes up about 1% of the human genome, and correctly identified Denisovan introgression in genomes from Asia and Oceania. But many ancient regions matched neither lineage. The researchers traced these segments to two distinct, previously uncharacterized lineages with different introgression timelines: a “ghost” lineage found in all modern human genomes, comprising roughly 0.5% to 1% of each individual’s genome, and a “super-archaic” lineage detected only in regions of Denisovan ancestry within genomes from Oceania, where Denisovan DNA reaches up to 4%.
“We discovered that about 2% of the modern human genome is from archaic hominins,” said Yulin Zhang, co-first author of the study. Arjun Biddanda, co-first author, noted that “These contributions are widespread throughout the genome, and ghost ancestry is detected even in regions previously thought to be intolerant of Neanderthal and Denisovan ancestry.”
Many of these archaic segments are enriched in genomic regions associated with immunity and metabolic function. Moorjani said she hopes expanding genome databases and additional Denisovan genome sequences will help detect further archaic lineages, adding that TRACE “should also work with other species.”