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Rapid evolution of primate type 2 immune response factors linked to asthma susceptibility

Matthew F. Barber, Elliot M. Lee, Hayden Griffin, Nels C. Elde
doi: https://doi.org/10.1101/080424
Matthew F. Barber
1Department of Human Genetics, University of Utah School of Medicine. Salt Lake City, UT, 84112, United States of America
2Present address: Institute of Ecology & Evolution, University of Oregon. Eugene, OR, 97403, United States of America
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Elliot M. Lee
1Department of Human Genetics, University of Utah School of Medicine. Salt Lake City, UT, 84112, United States of America
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Hayden Griffin
1Department of Human Genetics, University of Utah School of Medicine. Salt Lake City, UT, 84112, United States of America
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Nels C. Elde
1Department of Human Genetics, University of Utah School of Medicine. Salt Lake City, UT, 84112, United States of America
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  • For correspondence: nelde@genetics.utah.edu
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ABSTRACT

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted October 12, 2016.
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Rapid evolution of primate type 2 immune response factors linked to asthma susceptibility
Matthew F. Barber, Elliot M. Lee, Hayden Griffin, Nels C. Elde
bioRxiv 080424; doi: https://doi.org/10.1101/080424
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Rapid evolution of primate type 2 immune response factors linked to asthma susceptibility
Matthew F. Barber, Elliot M. Lee, Hayden Griffin, Nels C. Elde
bioRxiv 080424; doi: https://doi.org/10.1101/080424

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