The contribution of Neanderthal introgression to modern human traits

Abstract

Neanderthals, our closest extinct relatives, lived in western Eurasia from 400,000 years ago until they went extinct around 40,000 years ago. DNA retrieved from ancient specimens revealed that Neanderthals mated with modern human contemporaries. As a consequence, introgressed Neanderthal DNA survives scattered across the human genome such that 1-4% of the genome of present-day people outside Africa are inherited from Neanderthal ancestors. Patterns of Neanderthal introgressed genomic sequences suggest that Neanderthal alleles had distinct fates in the modern human genetic background. Some Neanderthal alleles facilitated human adaptation to new environments such as novel climate conditions, UV exposure levels and pathogens, while others had deleterious consequences. Here, we review the body of work on Neanderthal introgression over the past decade. We describe how evolutionary forces shaped the genomic landscape of Neanderthal introgression and highlight the impact of introgressed alleles on human biology and phenotypic variation.

Figure 1.

Neanderthal geographic range. Dating and location of some of the archaic hominin specimens for which nuclear ancient DNA is available are also shown. Asterisks (*) indicate genomes sequenced at high coverage. Created with BioRender.com

Figure 2:. Simplified demographic model illustrating inferred population relationships and admixture events among modern humans and archaic hominins.

Adapted from Nielsen et al. 2017 Nature. Events depicted in the schematic include (1) gene flow from early modern humans (MH) into Neanderthals^,,, (2) from a super-archaic hominin lineage into Denisovans^,, and (3) gene flow from a super-archaic hominin lineage into early modern humans in Africa^,–; (4) admixture events between Neanderthals and Denisovans in the Altai Mountains^,, also supported by the sequencing of the first generation offspring of a Neanderthal mother and a Denisovan father; (5) gene flow from Neanderthals into the ancestors of all non-Africans^,,,,, (6) putative gene flow from Neanderthals into the ancestors of East Asians^,, (represented by a dashed arrow), (7) back migration from Eurasia to Africa; and multiple Denisovan introgressions into the ancestors of (8–9) Oceanians ^–,,, and (10) East Asians. For simplicity we represent the multiple, distinct introgressing Denisovan-like lineages as arising from a single Denisovan source.

Figure 3.. The geographic and genomic landscape of Neanderthal introgression.

(A) Proportion of Neanderthal ancestry in geographically diverse populations. Reproduced with permission from Prüfer et al. (2017) Science. (B) Neanderthal introgressed genomic regions are depicted by colored ticks throughout the genomes of East Asians (red) and Europeans (blue). Introgressed deserts are large genomic regions (≥10 Mbp) depleted of Neanderthal introgression. Grey regions denote genome assembly gaps, and black ovals indicate the approximate position of each centromere. Reproduced with permission from Vernot & Akey (2014) Science. (C) Frequencies of Neanderthal introgressed haplotypes in East Asians (top), Europeans (middle), and South Asians (bottom). Positive selection after admixture with Neanderthals likely drove some of these haplotypes to high frequency. Gray dashed lines mark the 99th percentile. Haplotypes above the line are considered strong candidates for adaptive introgression. Large red dots indicate haplotypes with a significant phenotypic association. Reproduced with permission from Gittelman et al. (2016) Current Biology.

BOX 1 Figure. Morphological differences between Neanderthals and modern humans.

(A) Comparison of craniofacial features in Neanderthals and modern humans. (B) Example of non-taurodont and taurodont molars exhibiting enlarged pulp chambers. (C) Comparison of Neanderthal and modern human skeletal morphology. Features that are typically attributed to Neanderthals are labeled.

BOX 2 Figure

CT scans of Neanderthal (left) and modern human (right) crania exhibiting the elongated cranial shape characteristic of Neanderthals and the globular shape characteristic of modern humans.