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Analysis of Ancient DNA Reveals Ancestor to Present-day Asians, Native Americans

NEW YORK (GenomeWeb News) – Genetic analysis of remains from an early modern human unearthed from a cave in northern China suggests that humans living in that region about 40,000 years ago may be related to the ancestors of both modern-day Asians and Native Americans, researchers led by the Max Planck Institute for Evolutionary Anthropology's Svante Pääbo reported in an online, early Proceedings of the National Academy of Science paper this week.

Pääbo and his team extracted DNA from two leg bones from an anatomically modern human found in the Tianyuan Cave, located southwest of Beijing. Because the researchers could only isolate a small percentage of human DNA from the samples, they could not sequence the entire genome of the Tianyuan Cave individual. Instead, they focused on analyzing mitochondrial DNA, DNA from chromosome 21, and more than 3,000 polymorphic sites spread around the nuclear genome, and compared this individual's genome to those from modern humans from around the world as well as to Neandertal and Denisovan genomes.

"This individual lived during an important evolutionary transition when early modern humans, who shared certain features with earlier forms such as Neanderthals, were replacing Neanderthals and Denisovans, who later became extinct," Pääbo said in a statement.

Using a DNA capture approach, Pääbo and his colleagues isolated and then sequenced mtDNA and nuclear DNA from the Tianyuan individual.

For their mtDNA analysis, they sequenced libraries constructed from four extracts from two different leg bones using the Illumina GAII platform. By aligning the sequences to the reference human mtDNA genome, the researchers found that the consensus sequences from the four libraries were in agreement with each other. Then, using the library with the highest amount of mtDNA, they generated 35.6-fold coverage of the Tianyuan individual's mtDNA.

Ancient human DNA, though, is easily susceptible to contamination with modern human DNA. However, ancient DNA is marked by cytosine residue deamination at fragment ends, while modern DNA is not. The researchers reported that that pattern of deamination was seen in the Tianyuan DNA. Additionally, deep sequencing of the mtDNA indicated that it came from one source, giving further evidence that the researchers' sample was authentic.

Based on phylogenetic tree analysis comparing Tianyuan mtDNA to that of Neandertal and more than 300 modern humans, the researchers found that Tianyuan mtDNA fell within the variation seen in modern human DNA.

In particular, the Tianyuan individual has the characteristics of haplogroup R and its sub-group, haplogroup B, though the Tianyuan individual also has four substitutions that haplogroup B does not. From this, the researchers said that the Tianyuan individual has mtDNA that is ancestral to that of present-day haplogroup B. Today, mtDNA haplogroup B is found in Central Asian, Korean, Melanesian, Native American, Polynesian, Russian, and Taiwanese populations.

"The fact that an individual who lived in the Beijing area 40,000 [years] ago carried a mitochondrial genome that is potentially ancestral to mtDNAs in all these areas suggests that there is at least some population continuity from the earliest modern humans in East Asia to present-day populations in these areas," the researchers wrote.

To further support this idea, the researchers turned to nuclear DNA from the Tianyuan individual, examining portions of chromosome 21, which they sequenced to 1.75-fold coverage, and compared it to chromosome 21 sequences from 11 present-day humans from around the world and a Denisovan individual. Denisovans are an extinct group of ancient hominins who lived about 30,000 to 50,000 years ago.

By comparing substitutions in the chromosome 21 sequences, the researchers found that the Tianyuan sequence was more similar to present-day humans than to the Denisovan individual, and that it was more similar to sequences from present-day Eurasians than present-day Africans or Europeans.

Additionally, based on a maximum likelihood tree, they found that the Tianyuan sequence appears to be ancestral to all the Asian samples. The researchers could not, though, determine the relationship between the Tianyuan and Papuan individuals.

A prior study from Pääbo, published in Nature in 2010, found evidence of gene flow from the ancient Denisovan hominin group into the ancestors of present-day Melanesians, and so they examined whether there appeared to be any Denisovan or Neandertal gene flow into the Tianyuan individual.

To do so, Pääbo and his group expanded their examination of nuclear Tianyuan DNA to include about 1,700 SNPs where Neandertals and Densiovans differed from present-day humans and about 1,800 SNPs where Neandertals and Densiovans differed from each other. They found that the Tianyuan carried a portion of Neandertal DNA, though no Densiovan DNA. "The Tianyuan individual falls within the range of present-day Eurasian mainland populations," they added.

Pääbo and his team noted that their findings also were consistent with archaeological data on the spread of humans into Europe and Asia.

"More analyses of additional early modern humans across Eurasia will further refine our understanding of when and how modern humans spread across Europe and Asia," Pääbo said.