Some inheritances from Neanderthals might have left us with allergies. It all started when modern humans met Neanderthals in Europe. They started interbreeding and humans follow

Some inheritances from Neanderthals might have left us with allergies. It all started when modern humans met Neanderthals in Europe. They started interbreeding and humans following this exchange experienced gene variations that have increased the ability of those who carry them to ward off infection.

Evolution of the innate immune system serves as the body’s first line of defense against infection. The discoveries reported in two independent studies in the American Journal of Human Genetics on January 7 add to present evidence for a significant role for interspecies relations in human evolution and specifically in the first line of defense against infection.

Janet Kelso of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, said, We found that interbreeding with archaic humans, the Neanderthals and Denisovans, has influenced the genetic diversity in present-day genomes at three innate immunity genes belonging to the human Toll-like-receptor family.

Lluis Quintana-Murci of the Institut Pasteur and the CNRS in Paris further added that as compared to the remainder of the coding genome, these, and other, innate immunity genes present higher levels of Neanderthal ancestry.

Quintana-Murci and his colleagues relied on vast amounts of data available on present-day people from the 1000 Genomes Project together with the genome sequences of ancient hominins.

Ancient hominins, such as Neanderthal or Denisovans have given us one to six percent of modern Eurasian genomes. Both new studies highlight the functional importance of this inheritance on Toll-like receptor (TLR) genes–TLR1, TLR6, and TLR10. These TLR genes are expressed on the cell surface, where they detect and respond to components of bacteria, fungi, and parasites. These immune receptors are essential for extracting inflammatory and anti-microbial responses and for activating an adaptive immune response.

Quintana-Murci’s team focused on a list of 1,500 genes known to play a role in the innate immune system. They then analyzed patterns of genetic variation and evolutionary change in those regions relative to the rest of the genome at an unprecedented level of detail. Finally, they estimated the timing of the changes in innate immunity and the extent to which variation in those genes had been passed down from Neanderthals.

These investigations revealed little change over long periods of time for some innate-immunity genes, providing evidence of strong constraints. 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, they report.

But, Quintana-Murci says, the biggest surprise for them was to find that the TLR1-6-10 cluster is among the genes presenting the highest Neanderthal ancestry in both Europeans and Asians.

Kelso and her colleagues screened present-day human genomes for evidence of extended regions with high similarity to the Neanderthal and Denisovan genomes, then examined the prevalence of those regions in people from around the world. Those analyses led them to the same three TLR genes.

Two of those gene variants are most similar to the Neanderthal genome, whereas the third is most similar to the Denisovan genome.

Neanderthals had lived in Europe and Western Asia for around 200,000 years before the arrival of modern humans. They were likely well adapted to the local climate, foods, and pathogens. By interbreeding with these archaic humans, modern humans gained these advantageous adaptations.

Credit: Dannemann et al./American Journal of Human Genetics 2016