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Finding the genetic basis of these differences is not easy, as the immune response is comprised of a complex network of proteins that interact with one another to defend the body against infection. Here, we used population- and comparative genomics to study the evolutionary forces acting on the innate immune system in natural hosts of the avian influenza virus (AIV). For this purpose, we used a combination of hybrid capture, next- generation sequencing and published genomes to examine genetic diversity, divergence, and signatures of selection in 127 innate immune genes at a micro- and macroevolutionary time scale in 26 species of waterfowl. We show across multiple immune pathways (AIV-, toll-like-, and RIG-I -like receptors signalling pathways) that genes involved genes in pathogen detection (i.e., toll-like receptors) and direct pathogen inhibition (i.e., antimicrobial peptides and interferon-stimulated genes), as well as host proteins targeted by viral antagonist proteins (i.e., mitochondrial antiviral-signaling protein, [MAVS]) are more likely to be polymorphic, genetically divergent, and under positive selection than other innate immune genes. Our results demonstrate that selective forces vary across innate immune signaling signalling pathways in waterfowl, and we present candidate genes that may contribute to differences in susceptibility and resistance to infectious diseases in wild birds, and that may be manipulated by viruses. Our findings improve our understanding of the interplay between host genetics and pathogens, and offer the opportunity for new insights into pathogenesis and potential drug targets.<\/jats:p>","DOI":"10.1093\/molbev\/msac160","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T09:27:21Z","timestamp":1658827641000},"source":"Crossref","is-referenced-by-count":5,"title":["Comparative Genomics of the Waterfowl Innate Immune System"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-8634","authenticated-orcid":false,"given":"Elinor","family":"Jax","sequence":"first","affiliation":[{"name":"Department of Migration, Max Planck Institute of Animal Behavior , Radolfzell , Germany"},{"name":"Department of Biology, University of Konstanz , Konstanz , Germany"},{"name":"Department of Veterinary Medicine, University of Cambridge , Cambridge , United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-1463","authenticated-orcid":false,"given":"Paolo","family":"Franchini","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Konstanz , Konstanz , Germany"},{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-1591","authenticated-orcid":false,"given":"Vaishnovi","family":"Sekar","sequence":"additional","affiliation":[{"name":"Department of Biology, Lund University , Lund , Sweden"},{"name":"Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0335-9655","authenticated-orcid":false,"given":"Jente","family":"Ottenburghs","sequence":"additional","affiliation":[{"name":"Wildlife Ecology and Conservation Group, Wageningen University , Wageningen , The Netherlands"},{"name":"Forest Ecology and Forest Management Group, Wageningen University , Wageningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Monn\u00e9 Parera","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Konstanz , Konstanz , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman T","family":"Kellenberger","sequence":"additional","affiliation":[{"name":"Department of Plant Sciences, University of Cambridge , Cambridge , United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine E","family":"Magor","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Li Ka Shing Institute of Virology, University of Alberta , Edmonton , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Migration, Max Planck Institute of Animal Behavior , Radolfzell , Germany"},{"name":"Department of Biology, University of Konstanz , Konstanz , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Wikelski","sequence":"additional","affiliation":[{"name":"Department of Migration, Max Planck Institute of Animal Behavior , Radolfzell , Germany"},{"name":"Centre for the Advanced Study of Collective Behaviour, University of Konstanz , Konstanz , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H S","family":"Kraus","sequence":"additional","affiliation":[{"name":"Department of Migration, Max Planck Institute of Animal Behavior , Radolfzell , Germany"},{"name":"Department of Biology, University of Konstanz , Konstanz , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"2022080617393152700_msac160-B1","first-page":"2013","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2014"},{"issue":"4","key":"2022080617393152700_msac160-B2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"issue":"5","key":"2022080617393152700_msac160-B3","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1093\/molbev\/msq351","article-title":"Molecular evolution of the toll-like receptor multigene family in birds","volume":"28","author":"Alcaide","year":"2011","journal-title":"Mol Biol Evol"},{"key":"2022080617393152700_msac160-B4","author":"Andrews","year":"2010"},{"key":"2022080617393152700_msac160-B5","article-title":"Avian influenza cumulative number of confirmed human cases of avian influenza A\/(H5N1) reported to W. 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