Interbreeding between modern humans and Neanderthals in Europe may have enhanced modern humans’ ability to ward off infection, but it may also have increased susceptibility to allergies, say two reports published in the American Journal of Human Genetics.

[ancient peoples]Share on Pinterest
Archaic genes appear to boost our innate immunity.

Thousands of years ago, the environmental challenges facing modern humans dispersing out of Africa included novel foods, pathogens and a different climate, as well as other human forms.

Interspecies relations resulted in 1-6% of modern Eurasian genomes probably having been inherited from ancient hominins, such as Neanderthal or Denisovans.

Archaic alleles were added to the modern human gene pool, impacting the evolution of the innate immune system, the human body’s first line of defense against infection.

Meanwhile, infectious diseases have threatened humans throughout history, ravaging populations and causing high infant mortality and short life expectancy, especially before the discovery of hygiene, vaccines, antiseptics and antibiotics.

The human genetic makeup strongly influences an individual’s susceptibility to infectious disease and the chance of recovery; natural selection imposed by pathogens is therefore thought to have profoundly affected the patterns of variability of the human genome.

Indeed, purifying and positive selection are believed to have been pervasive among genes and functions related to immunity and host defense. Pathogen pressure is thought to have given rise to such selection, since many immunity-related genes present patterns of variation that strongly correlate with pathogen diversity.

The two new studies highlight the functional importance of this inheritance on Toll-like receptor (TLR) genes, TLR1, TLR6 and TLR10, immune receptors essential for eliciting inflammatory and anti-microbial responses and for activating an adaptive immune response.

The TLR genes are expressed on the cell surface, where they detect and respond to components of bacteria, fungi and parasites.

Lluis Quintana-Murci and colleagues from the Institut Pasteur and the CNRS in Paris, France, set out to explore how the innate immune system evolved over time.

Using modern data from the 1000 Genomes Project and the genome sequences of ancient hominins, they focused on a list of 1,500 genes known to be active in the innate immune system.

Next, they analyzed patterns of genetic variation and evolutionary change in the immune system relative to the rest of the genome.

Finally, they estimated the timing of changes in innate immunity and the extent to which variation in those genes were passed down from Neanderthals.

Some strongly constrained innate-immunity genes showed little change over long periods of time, whereas others appear to have been replaced by new variants that rose to prominence, possibly due to environmental shifts or disease.

Most of the adaptations appear to have occurred in the last 6,000-13,000 years, as human populations shifted from hunting and gathering to farming.

Interestingly, innate immunity genes present a higher average probability of Neanderthal ancestry than the rest of the coding genome.

Quintana-Murci says, “This highlights how important introgression events [the movement of genes across species] may have been in the evolution of the innate immunity system in humans.”

Janet Kelso and colleagues of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, set out to investigate the functional importance of genes inherited from archaic humans more broadly, but they reached the same conclusion as Quintana-Murci’s team.

They screened present-day human genomes to look for similarities with the Neanderthal and Denisovan genomes, then examined the prevalence of those similarities in people from around the world.

They arrived at the same three TLR genes but concluded that two of the variants approximate to the Neanderthal genome, whereas the third resembles the Denisovan genome.

The archaic gene variants were found to offer a selective advantage, being associated with greater activity of the TLR genes and greater reactivity to pathogens.

This sensitivity, suggest the researchers, might protect against infection, but it could also make modern-day people more prone to allergies.

Kelso says:

What has emerged from our study as well as from other work on introgression is that interbreeding with archaic humans does indeed have functional implications for modern humans, and that the most obvious consequences have been in shaping our adaptation to our environment: improving how we resist pathogens and metabolize novel foods.”

Neanderthals, she explains, lived in Europe and Western Asia for around 200,000 years before modern humans appeared and would, therefore, have been well adapted to the local climate, foods and pathogens. Interbreeding with Neanderthals meant that modern humans gained these advantageous adaptations.

Medical News Today recently reported on ancient DNA research revealing evidence about Ireland’s past.