‘Le Moustier Neanderthals, AMNH.’ (1920) By Charles Robert Knight.

Improving Our First Line of Defense: Neanderthal Genes

Our close cousins the Neanderthal and Denosivan people interbred with Homo sapiens and gave us genes that help us fight off infections, according to two new studies coming out this month. Unfortunately, those same genes that boosted our first-line immune response may have also made us modern people more susceptible to allergies.

A paper published in The American Journal of Human Genetics says that other studies have found that modern human immunity was boosted by interbreeding with what the authors call “archaic humans.” The genes the authors studied, human toll-like receptors, were possibly passed down to modern humans when they and Neanderthals interbred around 50,000 years ago.

Furthermore, Dr. Michael Dannemann et. al., wrote that the three human toll-like receptor genes in modern people that help us fight disease are among the top 1 percent of genes with the highest Neanderthal introgression. Introgression is the movement of genes from one species to another.

Forensic reconstruction of a Homo Neanderthalensis skull by Cicero Moraes

Forensic reconstruction of a Homo Neanderthalensis skull by Cicero Moraes ( CC BY SA 3.0 )

Researchers have estimated that 1 to 6 percent of modern Eurasian genes came from now extinct hominins, including the Denosivans and Neanderthals. The new study says other scholars have found that Neanderthal genes boosted the adaptive immune system, but these TLR receptor genes have given us an enhanced ability to fight infections through the innate immune response. The innate immune system is a first line of defense against pathogens and also detects germs and helps activate the adaptive immune response system.

The scientists describe what must have been a dramatic time in human history:

“Modern humans dispersing out of Africa were confronted with new environmental challenges including novel foods, pathogens, and a different climate,” wrote the authors, all three of whom are with the Max Planck Institute for Evolutionary Anthropology’s Department of Evolutionary Genetics. “They also encountered other human forms, and there is accumulating evidence that interbreeding with Neanderthals and Denisovans contributed alleles to the modern human gene pool.”

The top map shows the frequencies of Neanderthal-like haplotypes.

The top map shows the frequencies of Neanderthal-like haplotypes. The bottom map shows the prevalence of the three TLR genes in humans. The size of each pie is proportional to the number of individuals within a population. Core haplotypes (III, orange; IV, green; non-archaic core haplotypes V, VI, VIII, IX, blue) are colored. ( Dannemann, Andrés, & Kelso )

“Neanderthals lived in Europe and Western Asia for more than 200,000 years and were probably well adapted to the environment and local pathogens. It is therefore conceivable that admixture with Neanderthals contributed alleles that conferred a substantial immune advantage on modern humans expanding into Europe and Western Asia… At least two of these introgressed haplotypes appear to have been advantageous in certain modern human populations.”

But archaic genes are associated with increased susceptibility in modern people to allergies, the authors wrote.

They conclude: “Taken together, this suggests that the introgressed alleles might enhance innate immune surveillance and reactivity against certain pathogens, but that this might also have increased hypersensitivity to non-pathogenic allergens, resulting in allergic diseases in present-day people.”

The other paper, also in The American Journal of Human Genetics , is by researchers headed by Matthieu Deschamps of the Institut Pasteur. They write: “The burden of infectious diseases has been massive throughout human history, particularly before the advent of hygiene, vaccines, antiseptics, and antibiotics, when human populations were ravaged by illnesses that resulted in high childhood mortality and short life expectancy.” They explain that the Neanderthal genes were adaptive and essential for Europeans:

“Notably, among the genes presenting the highest Neanderthal ancestry, we find the TLR6-TLR1-TLR10 cluster, which also contains functional adaptive variation in Europeans. This study identifies highly constrained genes that fulfill essential, non-redundant functions in host survival and reveals others that are more permissive to change—containing variation acquired from archaic hominins or adaptive variants in specific populations—improving our understanding of the relative biological importance of innate immunity pathways in natural conditions.”

Neanderthal Ancestry of Innate Immunity Genes.

Neanderthal Ancestry of Innate Immunity Genes. (A) Comparison of the average introgression scores of innate immunity genes (IIGs) with respect to the remainder of protein-coding genes (non-IIGs) in European (EUR) and East Asian (ASN) populations. (B and C) Haplotypes of Neanderthal ancestry, red shadows highlight genomic regions containing innate immunity genes. ( Deschamps, M. et al .)

Thus, these researchers examined the exact same three genes that Dannemann et. al. studied and found the same result: a more powerful immune system thanks to the archaic humans’ genes.

Featured image: ‘Le Moustier Neanderthals, AMNH.’ (1920) By Charles Robert Knight. ( Public Domain ). Detail: A human neutrophil, which is a component of the immune system, ingests the MRSA germ. ( Public Domain )

By: Mark Miller

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