The human body is exposed to millions of pathogens on a daily basis. Usually we aren’t even aware of this near constant onslaught.

That’s because our body comes with three levels of defense against infection: The skin and mucus membrane, our innate immune system, and our adaptive immune system.

According to two new studies, we can thank our cavemen ancestors for part of our triple line of defense.

Two independent reports published in the American Journal of Human Genetics point to the mating of modern humans and archaic humans – Neanderthal and Denisovan – thousands of years ago.

This union gave us a critical component of our pathogen-fighting prowess. For some of us, it’s also likely the reason we have allergies.

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A Trio of Genes

Both reports say the evidence is found in three Toll-like Receptor (TLR) genes: TLR1, TLR6, and TLR10, which make the backbone of our innate immune system.

These set of non-specific defense mechanisms quickly kick into high gear when a germ enters the body.

When the two species got together modern humans inherited these genes. Scientists say further introgression, the back and forth transfer of genetic information from one species to another, solidified the foundation.

Michael Dannemann, PhD, a computational biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and lead author of one of the reports, said TLR genes are the livelihood of human survival.

“They are very important in our immune systems,” he said. “It’s the first line of defense.”

The three TLR genes essentially lay-in-wait on the surface of cells to detect and respond to bacteria, fungi, microbes, and other pathogens trying to enter the body. If they can’t successfully ward off an intruder, they give the go-ahead to the adaptive immune system to take a stab at it.

Two of the receptors highlighted in the study hail from Neanderthals, the other from Denisovans. Both Hominids roamed Europe and Western Asia for about 200,000 years before making contact with modern humans who entered the continents.

Only people of European and Asian descent inherited the archaic genes. Native sub-Sahara Africans did not because their ancestors never left the continent.

Scientists have known that up to 4 percent of the modern human genome comes from archaic humans. But not all humans carry these genes at the same rate.

These new studies reveal a range of frequency of the archaic TLR genes within the human genome. Europeans have up to 40 percent and Asians as much as 50 percent. The higher frequency likely represents their functionally importance, according to Dannemann.

“Neanderthals died out,” he said. “We did not.”

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Same Topic, Different Agendas

While both studies came to similar conclusions they started off with different agendas.

One of the studies used sequence variation from the 1000 Genomes project, the first of its kind to catalog the details of human genetic variations. It consists of about 3 million DNA base pairs.

The scientists in that study focused on 1,500 genes from the Genomes project and cross referenced them with the sequence of Neanderthal and Denisovan genes.

Dannemann and team also screened modern-day human genomes, but their charge was to find the functional significance of Neanderthal DNA in modern humans. They are the team that concluded TLR genes may also play a role in how susceptible people are to allergies in current times.

Anthony DeFranco, Ph.D., professor of microbiology and immunology at University of California San Francisco, said that the findings from both studies are interesting because it reveals the staying power of these specific TLR genes.

He makes the case that even after thousands of years of mating with other humans, the archaic DNA remains intact to this very day.

“Over time, you’d think the DNA would get diluted but it didn’t,” DeFranco said. “So it must have provided an advantage.”

He was also intrigued by the study’s inference of TLR genes on modern day allergies. Researchers have been looking for predispositions to allergies, according to DeFranco, and Dannemann’s team’s report may provide some insight in that realm of study.

The job of TLR genes is to fight off pathogens, he adds. However, when an environment doesn’t possess enough of a fertile playground for these receptors to do their work, they are forced to look elsewhere to complete their job.

“[The genes] protect you from infection, which was important back then,” De Franco said, “but [they] may make you more susceptible to allergies today. It’s a double-edged sword.”

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