Comparative Genomics of the Waterfowl Innate Immune System

Abstract

Animal species differ considerably in their ability to fight off infections. 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 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 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. 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 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.

Exploring the complexities of poultry respiratory microbiota: colonization, composition, and impact on health

“…The oropharyngeal cavity is the main and initial point of initial AIV replication, which is followed by replication in other sites including the gut [ 104 , 105 ]. The natural host of AIVs are waterfowls [ 106 ]. On the basis of pathogenicity, there are two major AIV pathotypes, high pathogenicity avian influenza (HPAI) viruses (e.g., H5N1) and low pathogenicity avian influenza (LPAI) viruses (e.g., H9N2) [ 107 ].…”

Comparative Investigation of Coincident Single Nucleotide Polymorphisms Underlying Avian Influenza Viruses in Chickens and Ducks

“…In recent decades, researchers have, therefore, made an extensive effort towards understanding AIV disease progression in chickens and ducks to investigate the causes of disease susceptibility and resistance. A considerable number of comparative analyses regarding the genetic repertoire, gene functions, and evolutionary selection related to immune responses in different bird species, including chickens and ducks, have been performed and published [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. In this regard, pattern recognition receptors (PRRs) have been put in the spotlight due to their rapid initiation of immune responses to pathogens such as AIVs [7,10,22].…”

“…A considerable number of comparative analyses regarding the genetic repertoire, gene functions, and evolutionary selection related to immune responses in different bird species, including chickens and ducks, have been performed and published [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. In this regard, pattern recognition receptors (PRRs) have been put in the spotlight due to their rapid initiation of immune responses to pathogens such as AIVs [7,10,22]. In particular, the susceptibility of chickens can be partly explained by their lack of the retinoic acid-inducible gene I (RIG-I) and the RIG-I binding protein RNF135 [7,9,11,[22][23][24][25][26][27].…”

“…In this regard, pattern recognition receptors (PRRs) have been put in the spotlight due to their rapid initiation of immune responses to pathogens such as AIVs [7,10,22]. In particular, the susceptibility of chickens can be partly explained by their lack of the retinoic acid-inducible gene I (RIG-I) and the RIG-I binding protein RNF135 [7,9,11,[22][23][24][25][26][27]. However, the absence of RIG-I in chickens is partly compensated for by the RIG-I-like receptor (RLR) MDA5 which is adapted in chickens to target small dsRNA [9,23,24,27].…”

“…Specifically, they highlight the strong early response of PRRs and ISGs in duck tissues combined with a decrease in expression of proinflammatory cytokines in the lung and key components of leukocyte recruitment and complement pathways in the intestine [41]. For comprehensive overviews of differential gene expression and innate immunity related to AIV infection in chickens and ducks, we refer to [6][7][8]22].…”