Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

More than a decade of genetic research on the Denisovans

Abstract

Denisovans, a group of now extinct humans who lived in Eastern Eurasia in the Middle and Late Pleistocene, were first identified from DNA sequences just over a decade ago. Only ten fragmentary remains from two sites have been attributed to Denisovans based entirely on molecular information. Nevertheless, there has been great interest in using genetic data to understand Denisovans and their place in human history. From the reconstruction of a single high-quality genome, it has been possible to infer their population history, including events of admixture with other human groups. Additionally, the identification of Denisovan DNA in the genomes of present-day individuals has provided insights into the timing and routes of dispersal of ancient modern humans into Asia and Oceania, as well as the contributions of archaic DNA to the physiology of present-day people. In this Review, we synthesize more than a decade of research on Denisovans, reconcile controversies and summarize insights into their population history and phenotype. We also highlight how our growing knowledge about Denisovans has provided insights into our own evolutionary history.

This is a preview of subscription content, access via your institution

Access options

Fig. 1: Location of samples attributed to Denisovans by molecular evidence.
Fig. 2: Relationships of Denisovans, Neandertals and modern humans reconstructed from nuclear DNA, mtDNA and the Y chromosome.
Fig. 3: Distribution of Denisovan ancestry today.
Fig. 4: Potential admixture histories between Denisovans and modern humans.
Fig. 5: Inferences made about the Denisovan phenotype.

Similar content being viewed by others

References

  1. Stoneking, M. An Introduction to Molecular Anthropology (Wiley, 2017).

  2. Fuhlrott, J. C. & Schaaffhausen, H. Über die Knochenfunde aus dem Neandertal bei Mettmann. Verhandlungen naturwissenschaftlicher-historischer Ver. preussisch Rheinl. Westfal. Correspondenz-Bl. 14, 50–52 (1857).

    Google Scholar 

  3. Meyer, M. et al. Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins. Nature 531, 504–507 (2016).

    Article  CAS  PubMed  Google Scholar 

  4. Higham, T. et al. The timing and spatiotemporal patterning of Neanderthal disappearance. Nature 512, 306–309 (2014).

    Article  CAS  PubMed  Google Scholar 

  5. Krause, J. et al. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature 464, 894–897 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Reich, D. et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060 (2010). This study describes the first genome sequence from a Denisovan, demonstrating that Denisovans were a sister group to Neandertals and that they admixed with the ancestors of Melanesians.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jacobs, Z. et al. Timing of archaic hominin occupation of Denisova Cave in southern Siberia. Nature 565, 594–599 (2019).

    Article  CAS  PubMed  Google Scholar 

  8. Green, R. E. et al. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell 134, 416–426 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sutikna, T. et al. Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia. Nature 532, 366–369 (2016).

    Article  CAS  PubMed  Google Scholar 

  10. Detroit, F. et al. A new species of Homo from the Late Pleistocene of the Philippines. Nature 568, 181–186 (2019).

    Article  CAS  PubMed  Google Scholar 

  11. Rizal, Y. et al. Last appearance of Homo erectus at Ngandong, Java, 117,000–108,000 years ago. Nature 577, 381–385 (2020).

    Article  CAS  PubMed  Google Scholar 

  12. Prüfer, K. et al. A high-coverage Neandertal genome from Vindija Cave in Croatia. Science 358, 655–658 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Reich, D. et al. Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania. Am. J. Hum. Genet. 89, 516–528 (2011). This study is the first to estimate Denisovan ancestry proportions in a broad set of populations from Asia and Oceania, hinting at Denisovan contact with modern humans in Island Southeast Asia and suggesting that Denisovans were widespread.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zavala, E. I. et al. Pleistocene sediment DNA reveals hominin and faunal turnovers at Denisova Cave. Nature 595, 399–403 (2021). By analysing the DNA recovered from 728 sediment samples from Denisova Cave, this study reconstructs the occupational history of Denisova Cave and reveals hominin and faunal turnovers. This provides evidence for alternating Denisovan and Neandertal presence at Denisova Cave over a period of around 200,000 years.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brown, S. et al. The earliest Denisovans and their cultural adaptation. Nat. Ecol. Evol. 6, 28–35 (2022).

    Article  PubMed  Google Scholar 

  16. Douka, K. et al. Age estimates for hominin fossils and the onset of the Upper Palaeolithic at Denisova Cave. Nature 565, 640–644 (2019).

    Article  CAS  PubMed  Google Scholar 

  17. Chen, F. et al. A late middle Pleistocene Denisovan mandible from the Tibetan Plateau. Nature 569, 409–412 (2019). This study reports the discovery of a late Middle Pleistocene hemi-mandible in the Baishiya Karst Cave that was inferred to be Denisovan based on ancient protein analysis.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang, D. et al. Denisovan DNA in Late Pleistocene sediments from Baishiya Karst cave on the Tibetan Plateau. Science 370, 584–587 (2020). This study reports the retrieval of Denisovan DNA from the sediment of Baishiya Karst Cave, thus confirming the presence of Denisovans in this cave.

    Article  CAS  PubMed  Google Scholar 

  19. Demeter, F. et al. A Middle Pleistocene Denisovan molar from the Annamite chain of northern Laos. Nat. Commun. 13, 2557 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang, C. H. et al. The first archaic Homo from Taiwan. Nat. Commun. 6, 6037 (2015).

    Article  CAS  PubMed  Google Scholar 

  21. Cooper, A. & Stringer, C. B. Did the Denisovans cross Wallace’s line? Science 342, 321–323 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Kaifu, Y. Archaic hominin populations in Asia before the arrival of modern humans: their phylogeny and implications for the “Southern Denisovans”. Curr. Anthropol. 58, S418–S433 (2017).

    Article  Google Scholar 

  23. Li, Z. Y. et al. Late Pleistocene archaic human crania from Xuchang, China. Science 355, 969–972 (2017).

    Article  CAS  PubMed  Google Scholar 

  24. Ni, X. et al. Massive cranium from Harbin in northeastern China establishes a new Middle Pleistocene human lineage. Innovation 2, 100130 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Meyer, M. et al. A high-coverage genome sequence from an archaic Denisovan individual. Science 338, 222–226 (2012). This study describes the first high-quality genome sequence from a Denisovan, which reveals extremely low levels of heterozygosity, refines the population split time between modern and archaic humans, and allows catalogues of the genetic changes between the two groups to be generated.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Li, H. & Durbin, R. Inference of human population history from individual whole-genome sequences. Nature 475, 493–496 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Prüfer, K. et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43–49 (2014).

    Article  PubMed  Google Scholar 

  28. Mafessoni, F. et al. A high-coverage Neandertal genome from Chagyrskaya Cave. Proc. Natl Acad. Sci. USA 117, 15132 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Skov, L. et al. Genetic insights into the social organization of Neanderthals. Nature 610, 519–525 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Slon, V. et al. The genome of the offspring of a Neanderthal mother and a Denisovan father. Nature 561, 113–116 (2018). This study describes the genome of Denisova 11, the first-generation offspring of a Neandertal mother and a Denisovan father, providing unequivocal evidence that Neandertals and Denisovans had met and mixed.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Peter, B. M. 100,000 years of gene flow between Neandertals and Denisovans in the Altai Mountains. Preprint at bioRxiv https://doi.org/10.1101/2020.03.13.990523 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kuhlwilm, M. et al. Ancient gene flow from early modern humans into eastern Neanderthals. Nature 530, 429–433 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Peyrégne, S., Kelso, J., Peter, B. M. & Pääbo, S. The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals. eLife https://doi.org/10.7554/eLife.75464 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Meyer, M. et al. A mitochondrial genome sequence of a hominin from Sima de los Huesos. Nature 505, 403–406 (2014).

    Article  CAS  PubMed  Google Scholar 

  35. Petr, M. et al. The evolutionary history of Neanderthal and Denisovan Y chromosomes. Science 369, 1653–1656 (2020).

    Article  CAS  PubMed  Google Scholar 

  36. Posth, C. et al. Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals. Nat. Commun. 8, 16046 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Peyrégne, S. et al. Nuclear DNA from two early Neandertals reveals 80,000 years of genetic continuity in Europe. Sci. Adv. 5, eaaw5873 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hubisz, M. J., Williams, A. L. & Siepel, A. Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph. PLoS Genet. 16, e1008895 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kim, B. Y. & Lohmueller, K. E. Selection and reduced population size cannot explain higher amounts of Neandertal ancestry in East Asian than in European human populations. Am. J. Hum. Genet. 96, 454–461 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Villanea, F. A. & Schraiber, J. G. Multiple episodes of interbreeding between Neanderthal and modern humans. Nat. Ecol. Evol. 3, 39–44 (2019).

    Article  PubMed  Google Scholar 

  41. Vernot, B. & Akey, J. M. Complex history of admixture between modern humans and Neandertals. Am. J. Hum. Genet. 96, 448–453 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wall, J. D. et al. Higher levels of neanderthal ancestry in East Asians than in Europeans. Genetics 194, 199–209 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Qin, P. & Stoneking, M. Denisovan Ancestry in East Eurasian and Native American populations. Mol. Biol. Evol. 32, 2665–2674 (2015).

    Article  CAS  PubMed  Google Scholar 

  44. Skoglund, P. & Jakobsson, M. Archaic human ancestry in East Asia. Proc. Natl Acad. Sci. USA 108, 18301–18306 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sankararaman, S., Mallick, S., Patterson, N. & Reich, D. The combined landscape of Denisovan and Neanderthal ancestry in present-day humans. Curr. Biol. 26, 1241–1247 (2016). This study generates a map of the Denisovan ancestry in the genomes of present-day humans, and also provides the first estimate of the time of admixture with Denisovans.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lu, D. et al. Ancestral origins and genetic history of Tibetan highlanders. Am. J. Hum. Genet. 99, 580–594 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Larena, M. et al. Philippine Ayta possess the highest level of Denisovan ancestry in the world. Curr. Biol. 31, 4219–4230 e4210 (2021). This study reports genetic data from 118 present-day ethnic groups of the Philippines and identifies that the Ayta Magbukon have the highest level of Denisovan ancestry worldwide.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Skov, L. et al. The nature of Neanderthal introgression revealed by 27,566 Icelandic genomes. Nature 582, 78–83 (2020).

    Article  CAS  PubMed  Google Scholar 

  49. Bergstrom, A. et al. Insights into human genetic variation and population history from 929 diverse genomes. Science https://doi.org/10.1126/science.aay5012 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Groube, L., Chappell, J., Muke, J. & Price, D. A 40,000 year-old human occupation site at Huon Peninsula, Papua New Guinea. Nature 324, 453–455 (1986).

    Article  CAS  PubMed  Google Scholar 

  51. Roberts, R. G., Jones, R. & Smith, M. A. Thermoluminescence dating of a 50,000-year-old human occupation site in northern Australia. Nature 345, 153–156 (1990).

    Article  Google Scholar 

  52. Barker, G. et al. The ‘human revolution’ in lowland tropical Southeast Asia: the antiquity and behavior of anatomically modern humans at Niah Cave (Sarawak, Borneo). J. Hum. Evol. 52, 243–261 (2007).

    Article  PubMed  Google Scholar 

  53. O’Connell, J. F. & Allen, J. The process, biotic impact, and global implications of the human colonization of Sahul about 47,000 years ago. J. Archaeol. Sci. 56, 73–84 (2015).

    Article  Google Scholar 

  54. Summerhayes, G. R. et al. Human adaptation and plant use in highland New Guinea 49,000 to 44,000 years ago. Science 330, 78–81 (2010).

    Article  CAS  PubMed  Google Scholar 

  55. Mijares, A. S. et al. New evidence for a 67,000-year-old human presence at Callao Cave, Luzon, Philippines. J. Hum. Evol. 59, 123–132 (2010).

    Article  PubMed  Google Scholar 

  56. Demeter, F. et al. Anatomically modern human in Southeast Asia (Laos) by 46 ka. Proc. Natl Acad. Sci. USA 109, 14375–14380 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. O’Connell, J. F. et al. When did Homo sapiens first reach Southeast Asia and Sahul? Proc. Natl Acad. Sci. USA 115, 8482–8490 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Clarkson, C. et al. Human occupation of northern Australia by 65,000 years ago. Nature 547, 306–310 (2017).

    Article  CAS  PubMed  Google Scholar 

  59. Jinam, T. A. et al. Discerning the origins of the Negritos, First Sundaland People: deep divergence and archaic admixture. Genome Biol. Evol. 9, 2013–2022 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Göllner, T. et al. Unveiling the genetic history of the Maniq, a primary hunter-gatherer society. Genome Biol. Evol. https://doi.org/10.1093/gbe/evac021 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Jacobs, G. S. et al. Multiple deeply divergent Denisovan ancestries in Papuans. Cell 177, 1010–1021 e1032 (2019). This study reports genomic data from 161 individuals from 14 island groups in Island Southeast Asia and New Guinea, revealing that Papuans carry DNA from two distinct Denisovan groups.

    Article  CAS  PubMed  Google Scholar 

  62. Malaspinas, A. S. et al. A genomic history of Aboriginal Australia. Nature 538, 207–214 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Larena, M. et al. Multiple migrations to the Philippines during the last 50,000 years. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2026132118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Choin, J. et al. Genomic insights into population history and biological adaptation in Oceania. Nature 592, 583–589 (2021). This study reports whole genomes for 317 individuals from 20 populations in the Pacific region, revealing differences in the proportion and origin of Denisovan ancestry in these populations.

    Article  CAS  PubMed  Google Scholar 

  65. Browning, S. R., Browning, B. L., Zhou, Y., Tucci, S. & Akey, J. M. Analysis of human sequence data reveals two pulses of archaic Denisovan admixture. Cell 173, 53–61.e9 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lipson, M. & Reich, D. A working model of the deep relationships of diverse modern human genetic lineages outside of Africa. Mol. Biol. Evol. 34, 889–902 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Ko, A. M. et al. Early Austronesians: into and out of Taiwan. Am. J. Hum. Genet. 94, 426–436 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Duggan, A. T. & Stoneking, M. Recent developments in the genetic history of East Asia and Oceania. Curr. Opin. Genet. Dev. 29, 9–14 (2014).

    Article  CAS  PubMed  Google Scholar 

  69. Wollstein, A. et al. Demographic history of Oceania inferred from genome-wide data. Curr. Biol. 20, 1983–1992 (2010).

    Article  CAS  PubMed  Google Scholar 

  70. Xu, S. et al. Genetic dating indicates that the Asian–Papuan admixture through Eastern Indonesia corresponds to the Austronesian expansion. Proc. Natl Acad. Sci. USA 109, 4574–4579 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. McColl, H. et al. The prehistoric peopling of Southeast Asia. Science 361, 88–92 (2018).

    Article  CAS  PubMed  Google Scholar 

  72. Skoglund, P. et al. Genomic insights into the peopling of the Southwest Pacific. Nature 538, 510–513 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lipson, M. et al. Population turnover in remote Oceania shortly after initial settlement. Curr. Biol. 28, 1157–1165.e7 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Mallick, S. et al. The Simons Genome Diversity Project: 300 genomes from 142 diverse populations. Nature 538, 201–206 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Witt, K. E., Villanea, F., Loughran, E., Zhang, X. & Huerta-Sanchez, E. Apportioning archaic variants among modern populations. Philos. Trans. R. Soc. Lond. B Biol. Sci. 377, 20200411 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Massilani, D. et al. Denisovan ancestry and population history of early East Asians. Science 370, 579–583 (2020). This study describes the Denisovan ancestry in early East Asians who lived 34 and 40 ka, showing that their Denisovan segments derive from the same admixture event(s) that contributed Denisovan DNA to present-day mainland Asians but are distinct from those in present-day Papuans and Indigenous Australians.

    Article  CAS  PubMed  Google Scholar 

  77. Skoglund, P. et al. Genetic evidence for two founding populations of the Americas. Nature 525, 104–108 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Moreno-Mayar, J. V. et al. Early human dispersals within the Americas. Science https://doi.org/10.1126/science.aav2621 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Raghavan, M. et al. Genomic evidence for the Pleistocene and recent population history of Native Americans. Science 349, aab3884 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Campelo Dos Santos, A. L. et al. Genomic evidence for ancient human migration routes along South America’s Atlantic coast. Proc. Biol. Sci. 289, 20221078 (2022).

    PubMed  PubMed Central  Google Scholar 

  81. Castro, E. S. M. A., Ferraz, T., Bortolini, M. C., Comas, D. & Hunemeier, T. Deep genetic affinity between coastal Pacific and Amazonian natives evidenced by Australasian ancestry. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2025739118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Goebel, T., Waters, M. R. & O’Rourke, D. H. The Late Pleistocene dispersal of modern humans in the Americas. Science 319, 1497–1502 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Sankararaman, S., Patterson, N., Li, H., Paabo, S. & Reich, D. The date of interbreeding between Neandertals and modern humans. PLoS Genet. 8, e1002947 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Fu, Q. et al. Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514, 445–449 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Fu, Q. et al. DNA analysis of an early modern human from Tianyuan Cave, China. Proc. Natl Acad. Sci. USA 110, 2223–2227 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yang, M. A. et al. 40,000-Year-old individual from Asia provides insight into early population structure in Eurasia. Curr. Biol. 27, 3202–3208.e9 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Huerta-Sanchez, E. et al. Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature 512, 194–197 (2014). By re-sequencing the region around the EPAS1 gene in Tibetans and Han Chinese, this study shows that variants in this gene that underlie adaptation to the hypoxic condition of the high-altitude Tibetan plateau were inherited from Denisovans or a related group.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang, X. et al. The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2020803118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Moreno-Mayar, J. V. et al. Terminal Pleistocene Alaskan genome reveals first founding population of Native Americans. Nature 553, 203–207 (2018).

    Article  CAS  PubMed  Google Scholar 

  90. Carlhoff, S. et al. Genome of a middle Holocene hunter-gatherer from Wallacea. Nature 596, 543–547 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Morwood, M. J. et al. Archaeology and age of a new hominin from Flores in eastern Indonesia. Nature 431, 1087–1091 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. Evans, A. R. et al. The maximum rate of mammal evolution. Proc. Natl Acad. Sci. USA 109, 4187–4190 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Sutikna, T. et al. The spatio-temporal distribution of archaeological and faunal finds at Liang Bua (Flores, Indonesia) in light of the revised chronology for Homo floresiensis. J. Hum. Evol. 124, 52–74 (2018).

    Article  PubMed  Google Scholar 

  94. Tucci, S. et al. Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia. Science 361, 511–516 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Stoneking, M. & Krause, J. Learning about human population history from ancient and modern genomes. Nat. Rev. Genet. 12, 603–614 (2011).

    Article  CAS  PubMed  Google Scholar 

  96. Teixeira, J. C. & Cooper, A. Using hominin introgression to trace modern human dispersals. Proc. Natl Acad. Sci. USA 116, 15327–15332 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Lahr, M. M. & Foley, R. Multiple dispersals and modern human origins. Evolut. Anthropol. Issues, N., Rev. 3, 48–60 (1994).

    Article  Google Scholar 

  98. Tassi, F. et al. Early modern human dispersal from Africa: genomic evidence for multiple waves of migration. Investig. Genet. 6, 13 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  99. Pagani, L. et al. Genomic analyses inform on migration events during the peopling of Eurasia. Nature 538, 238–242 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Skoglund, P. & Mathieson, I. Ancient genomics of modern humans: the first decade. Annu. Rev. Genomics Hum. Genet. 19, 381–404 (2018).

    Article  CAS  PubMed  Google Scholar 

  101. Sawyer, S. et al. Nuclear and mitochondrial DNA sequences from two Denisovan individuals. Proc. Natl Acad. Sci. USA 112, 15696–15700 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Slon, V. et al. A fourth Denisovan individual. Sci. Adv. 3, e1700186 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Viola, B. T. et al. A parietal fragment from Denisova Cave. Am. J. Phys. Anthropol. 168, 1–283 (2019).

    Google Scholar 

  104. Kayser, M. & Schneider, P. M. DNA-based prediction of human externally visible characteristics in forensics: motivations, scientific challenges, and ethical considerations. Forensic Sci. Int. Genet. 3, 154–161 (2009).

    Article  CAS  PubMed  Google Scholar 

  105. Liu, F. et al. Eye color and the prediction of complex phenotypes from genotypes. Curr. Biol. 19, R192–R193 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Burga, A. & Lehner, B. Predicting phenotypic variation from genotypes, phenotypes and a combination of the two. Curr. Opin. Biotechnol. 24, 803–809 (2013).

    Article  CAS  PubMed  Google Scholar 

  107. Brand, C. M., Colbran, L. L. & Capra, J. A. Predicting archaic hominin phenotypes from genomic data. Annu. Rev. Genomics Hum. Genet. 23, 591–612 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Wang, Y., Tsuo, K., Kanai, M., Neale, B. M. & Martin, A. R. Challenges and opportunities for developing more generalizable polygenic risk scores. Annu. Rev. Biomed. Data Sci. 5, 293–320 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Castellano, S. et al. Patterns of coding variation in the complete exomes of three Neandertals. Proc. Natl Acad. Sci. USA 111, 6666–6671 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Cerqueira, C. C. et al. Predicting Homo pigmentation phenotype through genomic data: from Neanderthal to James Watson. Am. J. Hum. Biol. 24, 705–709 (2012).

    Article  PubMed  Google Scholar 

  111. Perry, G. H., Kistler, L., Kelaita, M. A. & Sams, A. J. Insights into hominin phenotypic and dietary evolution from ancient DNA sequence data. J. Hum. Evol. 79, 55–63 (2015).

    Article  PubMed  Google Scholar 

  112. Fellows Yates, J. A. et al. The evolution and changing ecology of the African hominid oral microbiome. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2021655118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Henry, A. G., Brooks, A. S. & Piperno, D. R. Plant foods and the dietary ecology of Neanderthals and early modern humans. J. Hum. Evol. 69, 44–54 (2014).

    Article  PubMed  Google Scholar 

  114. Brand, C. M., Colbran, L. L. & Capra, J. A. Resurrecting the alternative splicing landscape of archaic hominins using machine learning. Nat. Ecol. Evol. 7, 939–953 (2023).

    Article  PubMed  Google Scholar 

  115. Condemi, S. et al. Blood groups of Neandertals and Denisova decrypted. PLoS ONE 16, e0254175 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975).

    Article  CAS  PubMed  Google Scholar 

  117. Carroll, S. B. Genetics and the making of Homo sapiens. Nature 422, 849–857 (2003).

    Article  CAS  PubMed  Google Scholar 

  118. Yan, S. M. & McCoy, R. C. Archaic hominin genomics provides a window into gene expression evolution. Curr. Opin. Genet. Dev. 62, 44–49 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Colbran, L. L. et al. Inferred divergent gene regulation in archaic hominins reveals potential phenotypic differences. Nat. Ecol. Evol. 3, 1598–1606 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Briggs, A. W. et al. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res. 38, e87 (2010).

    Article  PubMed  Google Scholar 

  121. Gokhman, D. et al. Reconstructing the DNA methylation maps of the Neandertal and the Denisovan. Science 344, 523–527 (2014).

    Article  CAS  PubMed  Google Scholar 

  122. Gokhman, D. et al. Reconstructing Denisovan anatomy using DNA methylation maps. Cell 179, 180–192.e10 (2019).

    Article  CAS  PubMed  Google Scholar 

  123. Weyer, S. & Paabo, S. Functional analyses of transcription factor binding sites that differ between present-day and archaic humans. Mol. Biol. Evol. 33, 316–322 (2016).

    Article  CAS  PubMed  Google Scholar 

  124. Uebbing, S. et al. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2007049118 (2021).

    Article  PubMed  Google Scholar 

  125. Weiss, C. V. et al. The cis-regulatory effects of modern human-specific variants. eLife https://doi.org/10.7554/eLife.63713 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Mora-Bermudez, F. et al. Longer metaphase and fewer chromosome segregation errors in modern human than Neanderthal brain development. Sci. Adv. 8, eabn7702 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Pinson, A. et al. Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science 377, eabl6422 (2022).

    Article  CAS  PubMed  Google Scholar 

  128. Dannemann, M. & Kelso, J. The contribution of Neanderthals to phenotypic variation in modern humans. Am. J. Hum. Genet. 101, 578–589 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Irving-Pease, E. K., Muktupavela, R., Dannemann, M. & Racimo, F. Quantitative human paleogenetics: what can ancient DNA tell us about complex trait evolution? Front. Genet. 12, 703541 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. McArthur, E., Rinker, D. C. & Capra, J. A. Quantifying the contribution of Neanderthal introgression to the heritability of complex traits. Nat. Commun. 12, 4481 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Vernot, B. et al. Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals. Science 352, 235–239 (2016). This study generates a map of the Denisovan ancestry in the genomes of present-day humans including 35 individuals from the Bismarck Archipelago.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Harris, K. & Nielsen, R. The genetic cost of Neanderthal introgression. Genetics 203, 881–891 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Steinrucken, M., Spence, J. P., Kamm, J. A., Wieczorek, E. & Song, Y. S. Model-based detection and analysis of introgressed Neanderthal ancestry in modern humans. Mol. Ecol. 27, 3873–3888 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Juric, I., Aeschbacher, S. & Coop, G. The strength of selection against Neanderthal introgression. PLoS Genet. 12, e1006340 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  135. Wei, X. et al. The lingering effects of Neanderthal introgression on human complex traits. eLife https://doi.org/10.7554/eLife.80757 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Beall, C. M. et al. Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders. Proc. Natl Acad. Sci. USA 107, 11459–11464 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Yi, X. et al. Sequencing of 50 human exomes reveals adaptation to high altitude. Science 329, 75–78 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Simonson, T. S. et al. Genetic evidence for high-altitude adaptation in Tibet. Science 329, 72–75 (2010).

    Article  CAS  PubMed  Google Scholar 

  139. Hackinger, S. et al. Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the Himalayas. Hum. Genet. 135, 393–402 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Brantingham, P. J. & Xing, G. Peopling of the northern Tibetan Plateau. World Archaeol. 38, 387–414 (2006).

    Article  Google Scholar 

  141. Gower, G., Picazo, P. I., Fumagalli, M. & Racimo, F. Detecting adaptive introgression in human evolution using convolutional neural networks. eLife https://doi.org/10.7554/eLife.64669 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Racimo, F., Marnetto, D. & Huerta-Sanchez, E. Signatures of Archaic adaptive introgression in present-day human populations. Mol. Biol. Evol. 34, 296–317 (2017).

    CAS  PubMed  Google Scholar 

  143. Racimo, F. et al. Archaic adaptive introgression in TBX15/WARS2. Mol. Biol. Evol. 34, 509–524 (2017).

    CAS  PubMed  Google Scholar 

  144. Bonfante, B. et al. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation. Sci. Adv. https://doi.org/10.1126/sciadv.abc6160 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Jagoda, E. et al. Disentangling immediate adaptive introgression from selection on standing introgressed variation in humans. Mol. Biol. Evol. 35, 623–630 (2018).

    Article  CAS  PubMed  Google Scholar 

  146. Mendez, F. L., Watkins, J. C. & Hammer, M. F. A haplotype at STAT2 Introgressed from neanderthals and serves as a candidate of positive selection in Papua New Guinea. Am. J. Hum. Genet. 91, 265–274 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Mendez, F. L., Watkins, J. C. & Hammer, M. F. Neandertal origin of genetic variation at the cluster of OAS immunity genes. Mol. Biol. Evol. 30, 798–801 (2013).

    Article  CAS  PubMed  Google Scholar 

  148. Mendez, F. L., Watkins, J. C. & Hammer, M. F. Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations. Mol. Biol. Evol. 29, 1513–1520 (2012).

    Article  CAS  PubMed  Google Scholar 

  149. Dannemann, M., Andres, A. M. & Kelso, J. Introgression of Neandertal- and Denisovan-like haplotypes contributes to adaptive variation in human Toll-like receptors. Am. J. Hum. Genet. 98, 22–33 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Deschamps, M. et al. Genomic signatures of selective pressures and introgression from archaic hominins at human innate immunity genes. Am. J. Hum. Genet. 98, 5–21 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Quach, H. et al. Genetic adaptation and neandertal admixture shaped the immune system of human populations. Cell 167, 643–656.e17 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Gittelman, R. M. et al. Archaic hominin admixture facilitated adaptation to out-of-Africa environments. Curr. Biol. 26, 3375–3382 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Nedelec, Y. et al. Genetic ancestry and natural selection drive population differences in immune responses to pathogens. Cell 167, 657–669.e21 (2016).

    Article  CAS  PubMed  Google Scholar 

  154. Sams, A. J. et al. Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans. Genome Biol. 17, 246 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Simonti, C. N. et al. The phenotypic legacy of admixture between modern humans and Neandertals. Science 351, 737–741 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Enard, D. & Petrov, D. A. Evidence that RNA viruses drove adaptive introgression between Neanderthals and modern humans. Cell 175, 360–371.e13 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Zeberg, H. & Paabo, S. A genomic region associated with protection against severe COVID-19 is inherited from Neandertals. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2026309118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Kerner, G., Patin, E. & Quintana-Murci, L. New insights into human immunity from ancient genomics. Curr. Opin. Immunol. 72, 116–125 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Abi-Rached, L. et al. The shaping of modern human immune systems by multiregional admixture with archaic humans. Science 334, 89–94 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Brucato, N. et al. Chronology of natural selection in Oceanian genomes. iScience 25, 104583 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Zammit, N. W. et al. Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity. Nat. Immunol. 20, 1299–1310 (2019).

    Article  CAS  PubMed  Google Scholar 

  162. Hsieh, P. et al. Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes. Science 366, eaax2083 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Natri, H. M. et al. Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago. PLoS Genet. 16, e1008749 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Natri, H. M. et al. Genetic architecture of gene regulation in Indonesian populations identifies QTLs associated with global and local ancestries. Am. J. Hum. Genet. 109, 50–65 (2022).

    Article  CAS  PubMed  Google Scholar 

  165. Vespasiani, D. M. et al. Denisovan introgression has shaped the immune system of present-day Papuans. PLoS Genet. 18, e1010470 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Nagai, A. et al. Overview of the BioBank Japan project: study design and profile. J. Epidemiol. 27, S2–S8 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Wei, C. Y. et al. Genetic profiles of 103,106 individuals in the Taiwan Biobank provide insights into the health and history of Han Chinese. NPJ Genom. Med. 6, 10 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Claw, K. G. et al. A framework for enhancing ethical genomic research with Indigenous communities. Nat. Commun. 9, 2957 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Villanea, F. A. & Witt, K. E. Underrepresented populations at the archaic introgression frontier. Front. Genet. 13, 821170 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  170. Paabo, S. The human condition — a molecular approach. Cell 157, 216–226 (2014).

    Article  PubMed  Google Scholar 

  171. Kuhlwilm, M. & Boeckx, C. A catalog of single nucleotide changes distinguishing modern humans from archaic hominins. Sci. Rep. 9, 8463 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Nuttle, X. et al. Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility. Nature 536, 205–209 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Giannuzzi, G. et al. The human-specific BOLA2 duplication modifies iron homeostasis and anemia predisposition in chromosome 16p11.2 autism individuals. Am. J. Hum. Genet. 105, 947–958 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Vicedomini, R., Polit, L., Condemi, S., Longo, L. & Carbone, A. Dietary adaptation in Neandertal, Denisovan and Sapiens revealed by gene copy number variation. Preprint at bioRxiv https://doi.org/10.1101/2021.10.30.466563 (2021).

    Article  Google Scholar 

  175. Ohta, T. The nearly neutral theory of molecular evolution. Annu. Rev. Ecol. Syst. 23, 263–286 (1992).

    Article  Google Scholar 

  176. Moriano, J. & Boeckx, C. Modern human changes in regulatory regions implicated in cortical development. BMC Genom. 21, 304 (2020).

    Article  CAS  Google Scholar 

  177. Srinivasan, S. et al. Genetic markers of human evolution are enriched in schizophrenia. Biol. Psychiatry 80, 284–292 (2016).

    Article  CAS  PubMed  Google Scholar 

  178. Gokhman, D. et al. Differential DNA methylation of vocal and facial anatomy genes in modern humans. Nat. Commun. 11, 1189 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Batyrev, D., Lapid, E., Carmel, L. & Meshorer, E. Predicted archaic 3D genome organization reveals genes related to head and spinal cord separating modern from archaic humans. Cells https://doi.org/10.3390/cells9010048 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  180. Przeworski, M. The signature of positive selection at randomly chosen loci. Genetics 160, 1179–1189 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  181. Przeworski, M. Estimating the time since the fixation of a beneficial allele. Genetics 164, 1667–1676 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  182. Racimo, F. Testing for ancient selection using cross-population allele frequency differentiation. Genetics 202, 733–750 (2016).

    Article  CAS  PubMed  Google Scholar 

  183. Racimo, F., Kuhlwilm, M. & Slatkin, M. A test for ancient selective sweeps and an application to candidate sites in modern humans. Mol. Biol. Evol. 31, 3344–3358 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Peyrégne, S., Boyle, M. J., Dannemann, M. & Prüfer, K. Detecting ancient positive selection in humans using extended lineage sorting. Genome Res. 27, 1563–1572 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  185. Schaefer, N. K., Shapiro, B. & Green, R. E. An ancestral recombination graph of human, Neanderthal, and Denisovan genomes. Sci. Adv. https://doi.org/10.1126/sciadv.abc0776 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  186. Stepanova, V. et al. Reduced purine biosynthesis in humans after their divergence from Neandertals. eLife https://doi.org/10.7554/eLife.58741 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  187. Petr, M., Paabo, S., Kelso, J. & Vernot, B. Limits of long-term selection against Neandertal introgression. Proc. Natl Acad. Sci. USA 116, 1639–1644 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Telis, N., Aguilar, R. & Harris, K. Selection against archaic hominin genetic variation in regulatory regions. Nat. Ecol. Evol. 4, 1558–1566 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  189. Silvert, M., Quintana-Murci, L. & Rotival, M. Impact and evolutionary determinants of Neanderthal introgression on transcriptional and post-transcriptional regulation. Am. J. Hum. Genet. 104, 1241–1250 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Jégou, B., Sankararaman, S., Rolland, A. D., Reich, D. & Chalmel, F. Meiotic genes are enriched in regions of reduced archaic ancestry. Mol. Biol. Evol. 34, 1974–1980 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  191. Chevy, E. T., Huerta-Sánchez, E. & Ramachandran, S. Integrating sex-bias into studies of archaic admixture on chromosome X. Preprint at bioRxiv https://doi.org/10.1101/2022.08.30.505789 (2022).

    Article  Google Scholar 

  192. Lai, C. S., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F. & Monaco, A. P. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523 (2001).

    Article  CAS  PubMed  Google Scholar 

  193. Vargha-Khadem, F., Watkins, K., Alcock, K., Fletcher, P. & Passingham, R. Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder. Proc. Natl Acad. Sci. USA 92, 930–933 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Fisher, S. E. & Scharff, C. FOXP2 as a molecular window into speech and language. Trends Genet. 25, 166–177 (2009).

    Article  CAS  PubMed  Google Scholar 

  195. Krause, J. et al. The derived FOXP2 variant of modern humans was shared with Neandertals. Curr. Biol. 17, 1908–1912 (2007).

    Article  CAS  PubMed  Google Scholar 

  196. Maricic, T. et al. A recent evolutionary change affects a regulatory element in the human FOXP2 gene. Mol. Biol. Evol. 30, 844–852 (2013).

    Article  CAS  PubMed  Google Scholar 

  197. Maricic, T. et al. Comment on “Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment”. Science 374, eabi6060 (2021).

    Article  PubMed  Google Scholar 

  198. Trujillo, C. A. et al. Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment. Science https://doi.org/10.1126/science.aax2537 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  199. Bennett, E. A. et al. Morphology of the Denisovan phalanx closer to modern humans than to Neanderthals. Sci. Adv. 5, eaaw3950 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Brown, S. et al. Identification of a new hominin bone from Denisova Cave, Siberia using collagen fingerprinting and mitochondrial DNA analysis. Sci. Rep. 6, 23559 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Iasi, L. N. M., Ringbauer, H. & Peter, B. M. An extended admixture pulse model reveals the limitations to human–Neandertal introgression dating. Mol. Biol. Evol. https://doi.org/10.1093/molbev/msab210 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  202. Green, R. E. et al. A draft sequence of the Neandertal genome. Science 328, 710–722 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Reich, D., Thangaraj, K., Patterson, N., Price, A. L. & Singh, L. Reconstructing Indian population history. Nature 461, 489–494 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Patterson, N. et al. Ancient admixture in human history. Genetics 192, 1065–1093 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  205. Bailey, S. E., Hublin, J. J. & Anton, S. C. Rare dental trait provides morphological evidence of archaic introgression in Asian fossil record. Proc. Natl Acad. Sci. USA 116, 14806–14807 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Bailey, S. E., Kupczik, K., Hublin, J. J. & Anton, S. C. Reply to Scott et al: a closer look at the 3-rooted lower second molar of an archaic human from Xiahe. Proc. Natl Acad. Sci. USA 117, 39–40 (2020).

    Article  CAS  PubMed  Google Scholar 

  207. Scott, G. R., Irish, J. D. & Martinon-Torres, M. A more comprehensive view of the Denisovan 3-rooted lower second molar from Xiahe. Proc. Natl Acad. Sci. USA 117, 37–38 (2020).

    Article  CAS  PubMed  Google Scholar 

  208. Setter, D. et al. VolcanoFinder: genomic scans for adaptive introgression. PLoS Genet. 16, e1008867 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Zhang, X. et al. MaLAdapt reveals novel targets of adaptive introgression from Neanderthals and Denisovans in worldwide human populations. Mol. Biol. Evol. https://doi.org/10.1093/molbev/msad001 (2023).

Download references

Acknowledgements

The authors thank B. Viola for providing the photographs of Denisovan remains used in Fig. 1 and Fig. 2, and R. Barr for help preparing Fig. 1. They thank S. Pääbo and M. Stoneking for many helpful discussions and for their comments on the manuscript. This project was funded by the Max Planck Society and the European Research Council (grant agreement no. 694707). V.S. acknowledges funding from the Alon Fellowship.

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Stéphane Peyrégne or Janet Kelso.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Genetics thanks Omer Gokcumen, who co-reviewed with Alber Aqil, and Mattias Jakobsson, Lluís Quintana-Murci and Shuhua Xu for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Glossary

Admixture

The interbreeding of individuals from two or more previously isolated populations.

Gene flow

The transfer of genetic material from one population to another through interbreeding.

Genetic drift

The random fluctuation in the frequency of genetic variants in a population over time.

Heterozygosity

The presence of two different alleles at a genomic locus.

Homozygous by descent

When both parents share a genomic segment from a recent common ancestor.

Introgression

The acquisition of genetic material from a genetically distinct population.

Melanesians

Present-day Indigenous inhabitants of New Guinea, the Solomon islands, New Caledonia, Fiji and Vanuatu. While the geographic descriptor ‘Melanesia’ should be avoided given its colonialist origin, the term ‘Melanesians’ is widely used by present-day people in the region to describe themselves.

Negritos

Several ethnic groups indigenous to the Andaman Islands, the Malaysian Peninsula, the Philippines and Thailand. Although the term has colonialist origins, these groups today self-identify as Negrito.

Negative selection

The selective removal of deleterious alleles in a population.

Positive selection

The selective increase in the frequency of a beneficial allele in a population.

Wallace’s line

An imaginary boundary separating the biogeographical regions of Asia and Australia.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peyrégne, S., Slon, V. & Kelso, J. More than a decade of genetic research on the Denisovans. Nat Rev Genet 25, 83–103 (2024). https://doi.org/10.1038/s41576-023-00643-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41576-023-00643-4

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing