穴居人基因使现代人免疫力提高却易过敏

When modern humans met Neanderthals in Europe and the two species began interbreeding many thousands of years ago, the exchange left humans with gene¹ variations that have increased the ability of those who carry them to ward² off infection. This inheritance from Neanderthals may have also left some people more prone³ to allergies⁴. 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 innate⁶ immune system, which serves as the body's first line of defense⁷ against infection. 

 

"We found that interbreeding with archaic⁸ humans--the Neanderthals and Denisovans--has influenced the genetic⁵ diversity in present-day genomes at three innate immunity⁹ genes¹⁰ belonging to the human Toll-like-receptor family," says Janet Kelso of the Max Planck Institute for Evolutionary¹¹ Anthropology¹² in Leipzig, Germany.

 

"These, and other, innate immunity genes present higher levels of Neanderthal ancestry¹³ 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 functional¹⁴ 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 components¹⁵ of bacteria, fungi¹⁶, and parasites¹⁷. These immune receptors are essential for eliciting¹⁸ inflammatory and anti-microbial responses and for activating¹⁹ 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 unprecedented²⁰ level of detail. Finally, they estimated the timing²¹ of the changes in innate immunity and the extent to which variation in those genes had been passed down from Neanderthals.

 

These investigations²² revealed little change over long periods of time for some innate-immunity genes, providing evidence of strong constraints²³. Other genes have undergone selective sweeps in which a new variant²⁴ came along and quickly rose to prominence²⁵, perhaps because of a shift in the environment or as a result of a disease epidemic²⁶. Most adaptations in protein-coding genes occurred in the last 6,000 to 13,000 years, as human populations shifted from hunting and gathering²⁷ to farming, they report.

分享到：