When modern humans met Neanderthals in Europe and the two species began interbreeding many thousands of years ago, the exchange left humans with gene variations that have increased the ability of those who carry them to ward off infection. This inheritance from Neanderthals may have also left some people more prone to allergies. The discoveries reported in two independent studies in the American Journal of Human Genetics on January 7 add to evidence for an important role for interspecies relations in human evolution and specifically in the evolution of the innate immune system, which serves as the body's first line of defense against infection. 

"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," says Janet Kelso of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

"These, and other, innate immunity genes present higher levels of Neanderthal ancestry than the remainder of the coding genome," adds Lluis Quintana-Murci of the Institut Pasteur and the CNRS in Paris. "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."

Earlier studies have shown that one to six percent of modern Eurasian genomes were inherited from ancient hominins, such as Neanderthal or Denisovans. 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 eliciting inflammatory and anti-microbial responses and for activating an adaptive immune response.

Quintana-Murci and his colleagues set out to explore the evolution of the innate immune system over time. They relied on vast amounts of data available on present-day people from the 1000 Genomes Project together with the genome sequences of ancient hominins. Quintana-Murci's team focused on a list of 1,500 genes known to play a role in the innate immune system. They then examined 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. Other genes have undergone selective sweeps in which a new variant came along and quickly rose to prominence, perhaps because of a shift in the environment or as a result of a disease epidemic. 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.