NEW YORK (GenomeWeb) – An international team led by investigators at the Max Planck Institute for Evolutionary Anthropology has sequenced the genome of a modern human man who lived in Siberia some 45,000 years ago, at a time when Neanderthals still resided in Europe and Western Asia.
In a paper published online in Nature, the researchers described this high-quality genome sequence — established with DNA from the femur bone of an "Ust'-Ishim" individual named for the western Siberian settlement where his remains were found — and its use for addressing everything from human mutation rates to mixing with Neanderthals.
"A big aim of our work over the past years has been to produce high-quality genome sequences for archaic and early modern humans," co-corresponding author Janet Kelso, an evolutionary genetics researcher at the Max Planck Institute for Evolutionary Anthropology, told GenomeWeb Daily News in an email message.
By sequencing such genomes and making them publicly available, she explained, the team hopes to facilitate more extensive study on modern human history.
For their analysis of the Ust'-Ishim femur bone, which was found on the banks of a Siberian river in 2008, the team used radiocarbon dating to put its age at between 43,210 and 46,880 years old.
The researchers then prepared several libraries from DNA extracted from the bone using methods designed to optimize ancient DNA extraction and focused in on libraries with high proportions of human DNA, which were sequenced using Illumina's HiSeq 2000 platform.
In the process, the group generated sequences that covered the autosomal chromosomes in the human genome to an average depth of 42-fold coverage. Coverage across the X and Y sex chromosomes was lower, coming in closer to 22-fold, on average.
From the variants identified in Ust'-Ishim's nuclear and mitochondrial genomes, researchers went on to look not only at his relationships to present-day populations in different parts of the world, but also to extinct archaic hominins.
For instance, Kelso and her colleagues identified stretches of sequences that match those found in the Neanderthal genome, consistent with the notion that modern humans mixed with Neanderthals before he was born roughly 45,000 year ago.
While the proportion of Neanderthal ancestry was similar to that detected in some present-day human populations in Eurasia, though, the Ust'-Ishim carried ancestry tracts that were far longer than those detected in human genomes today.
With this data, the team calculated that there was intermingling between his human ancestors and Neanderthals that stretched back an estimated 7,000 to 13,000 years before the Ust'-Ishim individual was born.
"Because the genome quality is so high and because this individual is so much closer to the time of introgression, we were able to estimate the timing of this admixture even more precisely than was previously possible," Kelso said.
That timing hints that the modern human-Neanderthal admixture events that have left their mark on non-African human genomes likely occurred too recently to be attributed to ancient Middle Eastern populations known as the Skhul and Qafzeh.
By comparing the new genome to genotyping data for hundreds of individuals from current human populations, the team found that Ust'-Ishim appeared to have non-African ancestry, apparently clustering at the crossroads of an ancient split between western European and East Asian populations.
"The finding that the Ust’-Ishim individual is equally closely related to present-day Asians and to 8,000- to 24,000-year-old individuals from western Eurasia, but not to present-day Europeans, is compatible with the hypothesis that present-day Europeans derive some of their ancestry from a population that did not participate in the initial dispersal of modern humans into Europe and Asia," the study's authors reasoned.
The genome also offered a refined look at mutation rates on human autosomal chromosomes and on the Y sex chromosome over tens of thousands of years, Kelso explained, noting that "the Ust’-Ishim man provides us with a completely new way to estimate the mutation rate in modern humans."
When they compared the ancient sequence to genomes from more than two-dozen present-day humans, the researchers observed mutation rates that roughly match those described from prior pedigree studies, but coincide less closely with alternative rates predicted from phylogenetic data.
"Using this ancient genome, we have been able to provide an independent estimate of the human mutation rate that agrees with the estimates from pedigree studies," Kelso said, "and suggests that between one and two mutations per year have accumulated in the genomes of populations in Europe and Asia since the Ust’-Ishim man lived."