Study uses ARGweaver-D algorithm to examine DNA from early human ancestors

A new study published in Plos Genetics suggests that DNA sequence analysis of Neanderthal and Denisovan genomes shows an interbreeding event that happened 200,000-300,000 years ago and opens up insights into the ancestors of modern humans.

The interbreeding between Neanderthals and modern humans that occurred approximately 50,000 years ago has received a lot of attention. That interbreeding left a "genetic legacy" as modern humans still have 1% to 3% of DNA from those populations, the paper states.

Here the authors found evidence of a much earlier interbreeding that has received less attention. The authors used the ARGweaver algorithm, also known as ARGweaver-D, to look into the genetic relationships between different ancient genomes, according to the journal's report.

The authors of the study, Melissa Hubisz, Amy Williams and Adam Siepel, note that they sampled ancestral recombination graphs (ARGs) and then parsed them to detect the archaic migration and interbreeding of extinct hominins and modern humans.

"We apply it to human, Neanderthal and Denisovan genomes, looking for signatures of older proposed migration events, including ancient humans into Neanderthal, and unknown archaic hominins into Denisovans," the report states. "We identify 3% of the Neanderthal genome that is putatively introgressed from ancient humans, and estimate that the gene flow occurred between 200,000 and 300,000 years ago."

The authors noted that they did not find any convincing evidence that there was any negative selection in the regions.

"Finally, we predict that 1% of the Denisovan genome was introgressed from an unsequenced but highly diverged archaic hominin ancestor," the authors found. "About 15% of these 'super-archaic' regions — comprising at least about 4Mb (genome size) —were, in turn, introgressed into modern humans and continue to exist in the genomes of people alive today."

The authors noted that other migration events were also detectable when they applied the ARGweaver-D algorithm. The authors applied the algorithm to the Neanderthals, Denisovans and two African humans and were able to identify 3% of the Neanderthal genome as human DNA and 1% of the Denisovan genome as human DNA.

"Given genome sequence data from a collection of individuals across multiple closely related populations or subspecies, ARGweaver-D can infer trees describing the genetic relationships among these individuals at every location along the genome, conditional on the demographic model," the authors state.

They note that Denisovans intermixed with early modern humans in Asia while Neanderthal DNA was found in Europeans, East Asians and other non-African populations.

It becomes harder to test for gene flow using standard methods as the network of interactions becomes more complicated, the authors noted. They suggest that even when there is evidence that supports the existence of gene flow, it's still hard to identify particular genomic regions.

The authors noted that they produced several sets of simulations and the rates of each of those events were chosen to produce similar levels of introgression that were already observed in the real data. That simulated data varied in demographic parameters, and all of the false positives and true positive rates were separated from one another.

"Altogether, given the number of gene flow events now documented among ancient hominins, it may be reasonable to assume that genetic exchange was likely whenever two groups overlapped in time and space," the authors note.