Denisovans: Primitive humans lived at high altitudes

[Celt_??]

"In 2010, archaeologists began studying the fossil and made a remarkable discovery: This high-altitude jaw is not like yours or mine. Proteins pried out of its ancient teeth revealed the mandible belonged to a Denisovan, an extinct human species related to Neanderthals. Jean-Jacques Hublin, an expert in human evolution at the Max Planck Institute for Evolutionary Anthropology in Germany, along with Dongju Zhang, an archaeologist at Lanzhou University in China, and an international team of collaborators published a study of the mandible on Wednesday in the journal Nature.....Their genes still echo through the human lineage. Modern humans, some of whom mated with Neanderthals, must have mated with Denisovans, too. The proportion of Deniosvan DNA in genomes of people native to Melanesia, for instance, reaches 6 percent. This discovery supports previous evidence that Denisovan DNA helped modern people thrive in the thin air of high altitudes. Certain Denisovan variants, such as a gene that allows the blood’s proteins to use oxygen more efficiently, are found in Sherpas and other people who live in the highest climates of Asia.....

"Because the monk removed the fossil from the cave, the study authors could not use the bone’s surroundings to determine a precise age. They said it was at least 160,000 years old, based on radiometric dating of a mineral crust stuck to the bone. That’s more than 100,000 years before the first signs of modern humans living in the Tibetan Plateau. Denisovan and Neanderthals share a lineage that branched off from the ancestor of modern humans about 700,000 years ago. The two sister species then split apart about 300,000 years later. It’s unclear when or why the Denisovans vanished, but a recent genomic analysis suggests they had children with modern humans as recently as 15,000 years ago.....


“The very early projected age of the fossil is exciting,” said John W. Olsen, a paleoanthropologist at the University of Arizona, who was not a part of this research. The jaw’s age indicates “that central and eastern Eurasia was a very complicated place in the late Middle Pleistocene, with respect to the story of human evolution.” The scientists could not pull DNA from the bone, so they used a technique called ancient protein analysis to establish whom it came from. Proteins can outlast a fossil’s DNA, said Frido Welker, a postdoctoral researcher in the Department of Human Evolution at the Max Planck Institute and a member of the study team. Welker examined the amino acids, the protein’s building blocks, of eight collagen proteins from the mandible. One amino acid found in modern humans was swapped out for a Denisovan alternate. The bone, Welker said, is definitely not a modern human “or some other kind of great ape.”

https://www.nature.com/articles/s41586-019-1139-x

https://www.washingtonpost.com/science/2019/05/01/jaw-mysterious-human-species-shows-early-embrace-high-life/?utm_term=.35d9de7f6d09


https://www.bbc.com/news/science-environment-48107498 (https://www.bbc.com/news/science-environment-48107498)

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[ThirdTerm]

The proportion of Deniosvan DNA in genomes of people native to Melanesia, for instance, reaches 6 percent. This discovery supports previous evidence that Denisovan DNA helped modern people thrive in the thin air of high altitudes. Certain Denisovan variants, such as a gene that allows the blood’s proteins to use oxygen more efficiently, are found in Sherpas and other people who live in the highest climates of Asia.....


Hu et al. (2017) previously studied Denisovan DNA and found a gene called EPAS1, which regulates the body’s production of hemoglobin, in high-altitude Tibetans. The Denisovan EPAS1 haplotype introgressed into the Tibetan population between 12 and 32 kya, influenced by strong positive selection in Tibetans which began between 7 and 28 kya. But unfortunately, Chen et al. (2019) failed to extract DNA from the Xiahe specimen and relied on ancient protein analysis to establish its non-human origin. Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA showed that Denisovans interbred with ancestral Tibetans in Tibet, from where Denisovan DNA may have spread to other East Asian populations. Tibetans and the Chinese frequently interacted until 9,000 years ago.

https://cdn.arstechnica.net/wp-content/uploads/2011/10/denisovan_map-4eaf0a7-intro.jpg




The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related population. We sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. We detected evidence of population structure between the ancestral Han and Tibetan subpopulations as early as 44 to 58 thousand years ago, but with high rates of gene flow until approximately 9 thousand years ago. The CMS test ranked EPAS1 and EGLN1 as the top two positive selection candidates, and in addition identified PTGIS, VDR, and KCTD12 as new candidate genes. The advantageous Tibetan EPAS1 haplotype shared many variants with the Denisovan genome, with an ancient gene tree divergence between the Tibetan and Denisovan haplotypes of about 1 million years ago. With the exception of EPAS1, we observed no evidence of positive selection on Denisovan-like haplotypes.

In summary, we performed a comprehensive genomic analysis on whole-genome sequence data from 27 Tibetan individuals. Our analyses detected evidence of population structure between the ancestral Han and Tibetan subpopulations beginning between 44 and 58 kya, although admixture rates between the two subpopulations remained high until around 9 kya. The Denisovan EPAS1 haplotype introgressed into the Tibetan population between 12 and 32 kya, and positive adaptive pressure on this haplotype began between 7 and 28 kya. We summarized the dates of important demographic events in Fig 5. The Our CMS test identified novel candidate genes for high-altitude adaptation including KCTD12, VDR and PTGIS, and also generated a list of candidate variants within the EPAS1 gene region. We estimated that 0.4% of the Tibetan genome are introgressed DNA from Denisovans, although EPAS1 is probably the only introgressed locus that was influenced by strong positive selection in Tibetans. Our study provided a rich genomic resource of the Tibetan population and generated hypotheses for future positive selection tests.

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006675

[Celt_??]

ThirdTerm, thank you for the excellent reference article. Very helpful - as well as the map.