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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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.
The authors declare no competing financial interests.
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.
Extended data figures and tables
Extended Data Figure 1 Three features used in the Conditional Random Field for predicting Neanderthal ancestry.
Top (feature 1), patterns of variation at a single SNP. Sites at which a panel of sub-Saharan-African individuals carry the ancestral allele and in which the sequenced Neanderthal and the test haplotype carry the derived allele are likely to be derived from Neanderthal gene flow. Middle (feature 2), haplotype divergence patterns. Genomic segments in which the divergence of the test haplotype to the sequenced Neanderthal is low, whereas the divergence to a panel of sub-Saharan-African individuals is high, are likely to be introgressed. Bottom (feature 3), we searched for segments that have a length consistent with what is expected from Neanderthal-to-modern-human gene flow approximately 2,000 generations ago, corresponding to a size of about 0.05 cM = (100 cM per Morgan)/(2,000 generations).
Extended Data Figure 2 Map of Neanderthal ancestry in 1000 Genomes European and east-Asian populations.
For each chromosome, we plot the fraction of alleles confidently inferred to be of Neanderthal origin (probability >90%) in non-overlapping 1-Mb windows in Europeans (red) and in east Asians (green). Black bars denote the coordinates of the centromeres. We plot traces in non-overlapping 10-Mb windows that pass filters. We label 10-Mb-scale windows that are deficient in Neanderthal ancestry (e1–e9 (e, European), a1–a17 (a, Asian)) (see Supplementary Information section 8 for details).
a, Example tiling path at the BNC2 locus on chromosome 9 in European individuals. Red, confidently inferred Neanderthal haplotypes in a subset of these individuals; blue, resulting tiling path. We identified Neanderthal haplotypes by scanning for runs of consecutive SNPs along a haplotype with a marginal probability >90% and requiring the haplotypes to be at least 0.02 cM long. b, Distribution of contig lengths obtained by constructing a tiling path across confidently inferred Neanderthal haplotypes. On merging Neanderthal haplotypes in each of the 1000 Genomes European and east-Asian populations, we reconstructed 4,437 Neanderthal contigs with median length 129 kb.
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Sankararaman, S., Mallick, S., Dannemann, M. et al. The genomic landscape of Neanderthal ancestry in present-day humans. Nature 507, 354–357 (2014). https://doi.org/10.1038/nature12961
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