Letter | Published:

The genomic landscape of Neanderthal ancestry in present-day humans

Nature volume 507, pages 354357 (20 March 2014) | Download Citation

Abstract

Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture1,2. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci1,3,4,5,6,7,8. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans9. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes10,11,12. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

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Acknowledgements

We thank A. Briggs, P. Moorjani, M. Przeworski, D. Presgraves and A. Williams for critical comments, and K. Kavanagh for help with Extended Data Fig. 2. We are grateful for support from the Presidential Innovation Fund of the Max Planck Society, NSF HOMINID grant 1032255 and NIH grant GM100233. S.S. was supported by a post-doctoral fellowship from the Initiative for the Science of the Human Past at Harvard University. D.R. is a Howard Hughes Medical Institute Investigator.

Author information

Affiliations

  1. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Sriram Sankararaman
    • , Swapan Mallick
    • , Nick Patterson
    •  & David Reich
  2. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA

    • Sriram Sankararaman
    • , Swapan Mallick
    • , Nick Patterson
    •  & David Reich
  3. Max Planck Institute for Evolutionary Anthropology, Leipzig 04103, Germany

    • Michael Dannemann
    • , Kay Prüfer
    • , Janet Kelso
    •  & Svante Pääbo
  4. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA

    • David Reich

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Contributions

S.S., N.P., S.P. and D.R. conceived of the study. S.S., S.M. M.D., K.P., J.K. and D.R. performed analyses. J.K., S.P., N.P. and D.R. supervised the study. S.S. and D.R. wrote the manuscript with help from all co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Sriram Sankararaman or David Reich.

The tiling path of confidently inferred Neanderthal haplotypes, as well as the Neanderthal introgression map, can be found at http://genetics.med.harvard.edu/reichlab/Reich_Lab/Datasets.html.

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    Supplementary Information

    This file contains Supplementary Figures, Supplementary Tables and Supplementary Text and Data - see Contents for more information.

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https://doi.org/10.1038/nature12961

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