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Ancient admixture from an extinct ape lineage into bonobos

Nature Ecology & Evolution volume 3, pages 957–965 (2019)Cite this article

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An Author Correction to this article was published on 14 May 2019

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Abstract

Admixture is a recurrent phenomenon in humans and other great ape populations. Genetic information from extinct hominins allows us to study historical interactions with modern humans and discover adaptive functions of gene flow. Here, we investigate whole genomes from bonobo and chimpanzee populations for signatures of gene flow from unknown archaic populations, finding evidence for an ancient admixture event between bonobos and a divergent lineage. This result reveals a complex population history in our closest living relatives, probably several hundred thousand years ago. We reconstruct up to 4.8% of the genome of this ‘ghost’ ape, which represents genomic data of an extinct great ape population. Genes contained in archaic fragments might confer functional consequences for the immunity, behaviour and physiology of bonobos. Finally, comparing the landscapes of introgressed regions in humans and bonobos, we find that a recurrent depletion of introgression is rare, suggesting that genomic incompatibilities arose seldom in these lineages.

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Fig. 1: Trees of putatively introgressed fragments.
Fig. 2: Analysis of putatively introgressed windows.
Fig. 3: Model of population history in Pan species with archaic gene flow into bonobos.
Fig. 4: Posterior values of the models used.
Fig. 5: Distribution of introgression across the genome.

Data availability

Sequence data from a previous study are publicly available under the accession code PRJEB15086 at the European Nucleotide Archive. Genotype data are available at http://biologiaevolutiva.org/tmarques/data/. Data pertaining to the results are in the Supplementary Information.

Change history

  • 14 May 2019

    In the version of this article originally published, a funding acknowledgement was missing for Tomas Maques-Bonet. The original funding statement was: “T.M.-B. was supported by MINECO BFU2014-55090-P (FEDER), a U01 MH106874 grant, the Howard Hughes International Early Career programme, Obra Social ‘La Caixa’ and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya.” It has been updated to: “T.M.-B. was supported by BFU2017-86471-P (MINECO/FEDER, UE), a U01 MH106874 grant, the Howard Hughes International Early Career programme, Obra Social ‘La Caixa’ and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880).” The error has been corrected in the HTML and PDF versions of this article.

References

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

    Article  CAS  Google Scholar 

  2. Reich, D. et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060 (2010).

    Article  CAS  Google Scholar 

  3. Hammer, M. F., Woerner, A. E., Mendez, F. L., Watkins, J. C. & Wall, J. D. Genetic evidence for archaic admixture in Africa. Proc. Natl Acad. Sci. USA 108, 15123–15128 (2011).

    Article  CAS  Google Scholar 

  4. Meyer, M. et al. A high coverage genome sequence from an archaic Denisovan individual. Science 338, 222–226 (2012).

    Article  CAS  Google Scholar 

  5. Vernot, B. & Akey, J. M. Resurrecting surviving Neandertal lineages from modern human genomes. Science 343, 1017–1021 (2014).

    Article  CAS  Google Scholar 

  6. Fu, Q. et al. An early modern human from Romania with a recent Neanderthal ancestor. Nature 524, 216–219 (2015).

    Article  CAS  Google Scholar 

  7. Vernot, B. et al. Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals. Science 352, 235–239 (2016).

    Article  CAS  Google Scholar 

  8. Xu, D. et al. Archaic hominin introgression in Africa contributes to functional salivary MUC7 genetic variation. Mol. Biol. Evol. 34, 2704–2715 (2017).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. 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  Google Scholar 

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

    Article  Google Scholar 

  13. 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).

    Article  CAS  Google Scholar 

  14. Huerta-Sanchez, E. et al. Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature 512, 194–197 (2014).

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  16. Brunet, M. et al. A new hominid from the Upper Miocene of Chad, Central Africa. Nature 418, 145–151 (2002).

    Article  CAS  Google Scholar 

  17. McBrearty, S. & Jablonski, N. G. First fossil chimpanzee. Nature 437, 105–108 (2005).

    Article  CAS  Google Scholar 

  18. Prado-Martinez, J. et al. Great ape genetic diversity and population history. Nature 499, 471–475 (2013).

    Article  CAS  Google Scholar 

  19. Hey, J. The divergence of chimpanzee species and subspecies as revealed in multipopulation isolation-with-migration analyses. Mol. Biol. Evol. 27, 921–933 (2010).

    Article  CAS  Google Scholar 

  20. Tung, J. & Barreiro, L. B. The contribution of admixture to primate evolution. Curr. Opin. Genet. Dev. 47, 61–68 (2017).

    Article  CAS  Google Scholar 

  21. De Manuel, M. et al. Chimpanzee genomic diversity reveals ancient admixture with bonobos. Science 354, 477–481 (2016).

    Article  CAS  Google Scholar 

  22. Kawamoto, Y. et al. Genetic structure of wild bonobo populations: diversity of mitochondrial DNA and geographical distribution. PLoS One 8, e59660 (2013).

    Article  CAS  Google Scholar 

  23. Takemoto, H., Kawamoto, Y. & Furuichi, T. How did bonobos come to range south of the Congo river? Reconsideration of the divergence of Pan paniscus from other Pan populations. Evol. Anthropol. 24, 170–184 (2015).

    Article  Google Scholar 

  24. Takemoto, H. et al. The mitochondrial ancestor of bonobos and the origin of their major haplogroups. PLoS One 12, e0174851 (2017).

    Article  Google Scholar 

  25. Myers Thompson, J. A. A model of the biogeographical journey from proto-Pan to Pan paniscus. Primates 44, 191–197 (2003).

    PubMed  Google Scholar 

  26. Skov, L. et al. Detecting archaic introgression using an unadmixed outgroup. PLoS Genet. 14, e1007641 (2018).

    Article  Google Scholar 

  27. Won, Y.-J. J. & Hey, J. Divergence population genetics of chimpanzees. Mol. Biol. Evol. 22, 297–307 (2005).

    Article  CAS  Google Scholar 

  28. Plagnol, V. & Wall, J. D. Possible ancestral structure in human populations. PLoS Genet. 2, e105 (2006).

    Article  Google Scholar 

  29. Wall, J. D., Lohmueller, K. E. & Plagnol, V. Detecting ancient admixture and estimating demographic parameters in multiple human populations. Mol. Biol. Evol. 26, 1823–1827 (2009).

    Article  CAS  Google Scholar 

  30. Hsieh, P. et al. Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies. Genome Res. 26, 291–300 (2016).

    Article  CAS  Google Scholar 

  31. Lachance, J. et al. Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse African hunter-gatherers. Cell 150, 457–469 (2012).

    Article  CAS  Google Scholar 

  32. Nye, J. et al. Selection in the introgressed regions of the chimpanzee genome. Genome Biol. Evol. 10, 1132–1138 (2018).

    Article  CAS  Google Scholar 

  33. Excoffier, L., Dupanloup, I., Huerta-Sánchez, E., Sousa, V. C. & Foll, M. Robust demographic inference from genomic and SNP data. PLoS Genet. 9, e1003905 (2013).

    Article  Google Scholar 

  34. Hey, J. et al. Phylogeny estimation by integration over isolation with migration models. Mol. Biol. Evol. 35, 2805–2818 (2018).

    PubMed  PubMed Central  Google Scholar 

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

    Article  Google Scholar 

  36. Besenbacher, S., Hvilsom, C., Marques-Bonet, T., Mailund, T. & Schierup, M. H. Direct estimation of mutations in great apes reconciles phylogenetic dating. Nat. Ecol. Evol. 3, 286–292 (2019).

    Article  Google Scholar 

  37. Rasmussen, M. D., Hubisz, M. J., Gronau, I. & Siepel, A. Genome-wide inference of ancestral recombination graphs. PLoS Genet. 10, e1004342 (2014).

    Article  Google Scholar 

  38. Prüfer, K. et al. The bonobo genome compared with the chimpanzee and human genomes. Nature 486, 527–531 (2012).

    Article  Google Scholar 

  39. Kuhlwilm, M. et al. Evolution and demography of the great apes. Curr. Opin. Genet. Dev. 41, 124–129 (2016).

    Article  CAS  Google Scholar 

  40. Sankararaman, S. et al. The genomic landscape of Neanderthal ancestry in present-day humans. Nature 507, 354–357 (2014).

    Article  CAS  Google Scholar 

  41. Nam, K. et al. Extreme selective sweeps independently targeted the X chromosomes of the great apes. Proc. Natl Acad. Sci. USA 112, 6413–6418 (2015).

    Article  CAS  Google Scholar 

  42. Steinrücken, 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  Google Scholar 

  43. Piccinni, M.-P. T cells in normal pregnancy and recurrent pregnancy loss. Reprod. Biomed. Online 13, 840–844 (2006).

    Article  CAS  Google Scholar 

  44. Han, S., Andrés, A. M., Marques-Bonet, T. & Kuhlwilm, M. Genetic variation in Pan species is shaped by demographic history and harbors lineage-specific functions. Genome Biol. Evol. https://doi.org/10.1093/gbe/evz047 (2019).

    Article  Google Scholar 

  45. Kuhlwilm, M. & Boeckx, C. Genetic differences between humans and other hominins contribute to the “human condition”. Preprint at https://www.biorxiv.org/content/10.1101/298950v1 (2018).

  46. Furuichi, T. Social interactions and the life history of female Pan paniscus in Wamba, Zaire. Int. J. Primatol. 10, 173–197 (1989).

    Article  Google Scholar 

  47. Cagan, A. et al. Natural selection in the great apes. Mol. Biol. Evol. 33, 3268–3283 (2016).

    Article  CAS  Google Scholar 

  48. Brawand, D. et al. The evolution of gene expression levels in mammalian organs. Nature 478, 343–348 (2011).

    Article  CAS  Google Scholar 

  49. Bouhassira, E. E. et al. An alanine-to-threonine substitution in protein 4.2 cDNA is associated with a Japanese form of hereditary hemolytic anemia (protein 4.2NIPPON). Blood 79, 1846–1854 (1992).

    CAS  PubMed  Google Scholar 

  50. Loomis, M. R. in Zoo and Wild Animal Medicine 5th edn (eds Fowler, M. E. & Miller, R. E.) 381–397 (Saunders (Elsevier Science), 2003).

  51. Cyrklaff, M. et al. Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes. Science 334, 1283–1286 (2011).

    Article  CAS  Google Scholar 

  52. Dannemann, M., Andrés, 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  Google Scholar 

  53. Frazer, J. K. et al. Identification of centerin: a novel human germinal center B cell-restricted serpin. Eur. J. Immunol. 30, 3039–3048 (2000).

    Article  CAS  Google Scholar 

  54. Suzuki, K. et al. A novel glycosylphosphatidyl inositol-anchored protein on human leukocytes: a possible role for regulation of neutrophil adherence and migration. J. Immunol. 162, 4277–4284 (1999).

    CAS  PubMed  Google Scholar 

  55. Hernandez-Rodriguez, J. et al. The impact of endogenous content, replicates and pooling on genome capture from faecal samples. Mol. Ecol. Resour. 18, 319–333 (2017).

    Article  Google Scholar 

  56. Paten, B. et al. Genome-wide nucleotide-level mammalian ancestor reconstruction. Genome Res. 18, 1829–1843 (2008).

    Article  CAS  Google Scholar 

  57. Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).

    Article  CAS  Google Scholar 

  58. Lawrence, M., Gentleman, R. & Carey, V. rtracklayer: an R package for interfacing with genome browsers. Bioinformatics 25, 1841–1842 (2009).

    Article  CAS  Google Scholar 

  59. R Core Development Team R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2015).

  60. Vernot, B. freezing-archer (2016), GitHub repository, https://github.com/bvernot/freezing-archer.

  61. Lawrence, M. et al. Software for computing and annotating genomic ranges. PLoS Comput. Biol. 9, e1003118 (2013).

    Article  CAS  Google Scholar 

  62. Haider, S. et al. A bedr way of genomic interval processing. Source Code Biol. Med. 11, 14 (2016).

    Article  Google Scholar 

  63. Wood, S. N. Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models. J. R. Stat. Soc. Ser. B 73, 3–36 (2011).

    Article  Google Scholar 

  64. Hudson, R. Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinformatics 18, 337–338 (2002).

    Article  CAS  Google Scholar 

  65. Kong, A. et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature 488, 471–475 (2012).

    Article  CAS  Google Scholar 

  66. Langergraber, K. E. et al. Generation times in wild chimpanzees and gorillas suggest earlier divergence times in great ape and human evolution. Proc. Natl Acad. Sci. USA 109, 15716–15721 (2012).

    Article  CAS  Google Scholar 

  67. Csilléry, K., François, O. & Blum, M. G. B. abc: an R package for approximate Bayesian computation (ABC). Methods Ecol. Evol. 3, 475–479 (2012).

    Article  Google Scholar 

  68. Stevison, L. S. et al. The time-scale of recombination rate evolution in great apes. Mol. Biol. Evol. 33, 928–945 (2016).

    Article  CAS  Google Scholar 

  69. Kelleher, J., Etheridge, A. M. & McVean, G. Efficient coalescent simulation and genealogical analysis for large sample sizes. PLoS Comput. Biol. 12, e1004842 (2016).

    Article  Google Scholar 

  70. Schliep, K. P. phangorn: phylogenetic analysis in R. Bioinformatics 27, 592–593 (2011).

    Article  CAS  Google Scholar 

  71. Jombart, T. & Ahmed, I. adegenet 1.3-1: new tools for the analysis of genome-wide SNP data. Bioinformatics 27, 3070–3071 (2011).

    Article  CAS  Google Scholar 

  72. Paradis, E. pegas: an R package for population genetics with an integrated–modular approach. Bioinformatics 26, 419–420 (2010).

    Article  CAS  Google Scholar 

  73. MacArthur, J. et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 45, D896–D901 (2017).

    Article  CAS  Google Scholar 

  74. Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).

    Article  Google Scholar 

  75. Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).

    Article  CAS  Google Scholar 

  76. Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2. Genome Biol. 15, 550 (2014).

    Article  Google Scholar 

  77. Pfeifer, B., Wittelsbürger, U., Ramos-Onsins, S. E. & Lercher, M. J. PopGenome: an efficient Swiss army knife for population genomic analyses in R. Mol. Biol. Evol. 31, 1929–1936 (2014).

    Article  CAS  Google Scholar 

  78. Kimura, M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J. Mol. Evol. 16, 111–120 (1980).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. M. Andres, B. Vernot and L. J. Kuhlwilm for comments and discussion, and M. de Manuel for help with the data. M.K. was supported by a DFG fellowship (KU 3467/1-1). V.C.S. was supported by the Fundação para a Ciência e a Tecnologia (project UID/BIA/00329/2013) and EU Horizon 2020 programme (Marie Skłodowska-Curie grant 799729). L.E. was supported by the Swiss National Science Foundation (number 310030B-166605). T.M.-B. was supported by BFU2017-86471-P (MINECO/FEDER, UE), a U01 MH106874 grant, the Howard Hughes International Early Career programme, Obra Social "La Caixa" and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880).

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Authors and Affiliations

  1. Institut de Biologia Evolutiva, (CSIC-Universitat Pompeu Fabra), Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain

    Martin Kuhlwilm, Sojung Han & Tomas Marques-Bonet

  2. Centre for Ecology, Evolution and Environmental Changes, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal

    Vitor C. Sousa

  3. Institute of Ecology and Evolution, University of Berne, Berne, Switzerland

    Vitor C. Sousa & Laurent Excoffier

  4. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    Laurent Excoffier

  5. National Centre for Genomic Analysis–Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain

    Tomas Marques-Bonet

  6. Institucio Catalana de Recerca i Estudis Avançats, Barcelona, Spain

    Tomas Marques-Bonet

  7. Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain

    Tomas Marques-Bonet

Authors
  1. Martin Kuhlwilm
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  4. Laurent Excoffier
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Contributions

M.K., S.H., V.C.S. and L.E. analysed the data. M.K. and T.M.-B. wrote the manuscript.

Corresponding authors

Correspondence to Martin Kuhlwilm or Tomas Marques-Bonet.

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Supplementary information

Supplementary Information

Supplementary methods and analysis, Supplementary Figures 1–32

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Supplementary Tables

Supplementary Tables 1–21

Supplementary Data

Principal component analysis (PCA) of putatively introgressed fragments.

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Kuhlwilm, M., Han, S., Sousa, V.C. et al. Ancient admixture from an extinct ape lineage into bonobos. Nat Ecol Evol 3, 957–965 (2019). https://doi.org/10.1038/s41559-019-0881-7

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