PT  - JOURNAL ARTICLE
AU  - Matthew F. Barber
AU  - Elliot M. Lee
AU  - Hayden Griffin
AU  - Nels C. Elde
TI  - Rapid evolution of primate type 2 immune response factors linked to asthma susceptibility
AID  - 10.1101/080424
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 080424
4099  - http://biorxiv.org/content/early/2016/10/12/080424.short
4100  - http://biorxiv.org/content/early/2016/10/12/080424.full
AB  - Host immunity pathways evolve rapidly in response to antagonism by pathogens. Microbial infections can also trigger excessive inflammation that contributes to diverse autoimmune disorders including asthma, lupus, diabetes, and arthritis. Definitive links between immune system evolution and human autoimmune disease remain unclear. Here we provide evidence that several components of the type 2 immune response pathway have been subject to recurrent positive selection in the primate lineage. Notably, rapid evolution of the central immune regulator IL13 corresponds to a polymorphism linked to asthma susceptibility in humans. We also find evidence of accelerated amino acid substitutions as well as repeated gene gain and loss events among eosinophil granule proteins, which act as toxic antimicrobial effectors that promote asthma pathology by damaging airway tissues. These results support the hypothesis that evolutionary conflicts with pathogens promote tradeoffs for increasingly robust immune responses during animal evolution. Our findings are also consistent with the view that natural selection has contributed to the spread of autoimmune disease alleles in humans.