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Two new papers in the American Journal of Human Genetics document how we should thank archaic humans like Neandertals and Denisovans for our allergies and boosted immune systems. Both studies highlight the functional importance of three inherited of Toll-like receptor genes; TLR1, TLR6, and TLR10. These toll like receptors respond to antigens from bacteria, fungi, and parasites and elicit an inflammatory response, ultimately activating the adaptive immune system.

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In the first paper, the researchers compared 1,500 genes known to play a role in the innate immune system from the 1,000 Genomes Project and contrasted it with the genomes of ancient humans. They looked for patterns in variation and change, looking at the timing of change.Most adaptations in protein-coding genes occurred in the last 6,000 to 13,000 years, as human populations shifted from hunting and gathering to farming. Some underwent very little change, indicating constraints. Others have undergone quick selective sweeps likely as a process of selection. The biggest surprise was that the TLR1-6-10 cluster is among the genes presenting the highest Neanderthal ancestry in both Europeans and Asians.

The scope of the second paper was to understand the function of inherited archaic genes. To do so, also screened present-day human genomes for evidence of extended regions with high similarity to the Neanderthal and Denisovan genomes. They then examined the prevalence of those regions in people from around the world which led to the same three TLR gene and these introgressed variants offered a selective advantage. The archaic-like variants are thought to increase activity to pathogens… Which in turn may have given greater protection against infection, but also increased the susceptibility of modern-day people to allergies. Certainly possible as Neandertals were living in Eurasia for 200,000 years before humans and had already well exposed and adapted to the local Eurasian pathogens. And by interbreeding with these archaic humans, modern humans gained these advantageous adaptations.

American Journal of Human Genetics, Deschamps et al.: “Genomic Signatures of Selective Pressures and Introgression from Archaic Hominins at Human Innate Immunity Genes” dx.doi.org/10.1016/j.ajhg.2015.11.014

American Journal of Human Genetics, Dannemann et al.: “Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors” dx.doi.org/10.1016/j.ajhg.2015.11.015

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