Modern Human Introgression Into Neanderthal DNA

Altai Neanderthals had significant (6%) modern human admixture from admixture events as much as 250,000 years ago (at the very dawn of the modern human species). Thus, gene flow went both ways between Neanderthals and modern humans. These genes mostly reduced the selective fitness of the hybrid Neanderthals.

Neanderthal admixture in sub-Saharan Africans, meanwhile, is due to Eurasian back migration to Africa.

Highlights 

• Anatomically modern human-to-Neanderthal introgression occurred ∼250,000 years ago

• ∼6% of the Altai Neanderthal genome was inherited from anatomically modern humans

• Recent non-African admixture brought Neanderthal ancestry to some African groups

• Modern human alleles were deleterious to Neanderthals

Summary

Comparisons of Neanderthal genomes to anatomically modern human (AMH) genomes show a history of Neanderthal-to-AMH introgression stemming from interbreeding after the migration of AMHs from Africa to Eurasia. 

All non-sub-Saharan African AMHs have genomic regions genetically similar to Neanderthals that descend from this introgression. Regions of the genome with Neanderthal similarities have also been identified in sub-Saharan African populations, but their origins have been unclear. 

To better understand how these regions are distributed across sub-Saharan Africa, the source of their origin, and what their distribution within the genome tells us about early AMH and Neanderthal evolution, we analyzed a dataset of high-coverage, whole-genome sequences from 180 individuals from 12 diverse sub-Saharan African populations. 

In sub-Saharan African populations with non-sub-Saharan African ancestry, as much as 1% of their genomes can be attributed to Neanderthal sequence introduced by recent migration, and subsequent admixture, of AMH populations originating from the Levant and North Africa. 

However, most Neanderthal homologous regions in sub-Saharan African populations originate from migration of AMH populations from Africa to Eurasia ∼250 kya, and subsequent admixture with Neanderthals, resulting in ∼6% AMH ancestry in Neanderthals. These results indicate that there have been multiple migration events of AMHs out of Africa and that Neanderthal and AMH gene flow has been bi-directional. 

Observing that genomic regions where AMHs show a depletion of Neanderthal introgression are also regions where Neanderthal genomes show a depletion of AMH introgression points to deleterious interactions between introgressed variants and background genomes in both groups—a hallmark of incipient speciation.

Daniel N. Harris, et al., "Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals" Current Biology (October 13, 2023). DOI:https://doi.org/10.1016/j.cub.2023.09.066

A popular media discussion of the paper explains that:

[T]hey compared the modern human genomes to a genome belonging to a Neanderthal who lived approximately 120,000 years ago. For this comparison, the team developed a novel statistical method that allowed them to determine the origins of the Neanderthal-like DNA in these modern sub-Saharan populations, whether they were regions that Neanderthals inherited from modern humans or regions that modern humans inherited from Neanderthals and then brought back to Africa.

They found that all of the sub-Saharan populations contained Neanderthal-like DNA, indicating that this phenomenon is widespread. In most cases, this Neanderthal-like DNA originated from an ancient lineage of modern humans that passed their DNA on to Neanderthals when they migrated from Africa to Eurasia around 250,000 years ago. As a result of this modern human-Neanderthal interbreeding, approximately 6% of the Neanderthal genome was inherited from modern humans.

In some specific sub-Saharan populations, the researchers also found evidence of Neanderthal ancestry that was introduced to these populations when humans bearing Neanderthal genes migrated back into Africa. Neanderthal ancestry in these sub-Saharan populations ranged from 0 to 1.5%, and the highest levels were observed in the Amhara from Ethiopia and Fulani from Cameroon.