Abstract
Two key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ultimately activates interferon-stimulated genes (ISGs). While in rare cases RIG-I gene loss has been detected in mammalian and avian species, most notably in the chicken, MDA5 pseudogenization has only been detected once in mammals. We have screened over a hundred publicly available avian genome sequences and describe an independent disruption of MDA5 in two unrelated avian lineages, the storks (Ciconiiformes) and the rallids (Gruiformes). The results of our RELAX analysis confirmed the absence of negative selection in the MDA5 pseudogene. In contrast to our prediction, we have shown, using multiple dN/dS-based approaches, that the MDA5 loss does not appear to have resulted in any compensatory evolution in the RIG-I gene, which may partially share its ligand-binding specificity. Together, our results indicate that the MDA5 pseudogenization may have important functional effects on immune responsiveness in these two avian clades.
Highlights
Genome evolution in vertebrates is strongly influenced by their pathogens, including viruses [1,2]
In order to better understand the evolution of avian RIG-I-like receptors (RLR) genes, we first collected a comprehensive set of melanoma differentiationassociated protein 5 (MDA5) coding sequences from various bird species
Besides the already annotated gene records in the National Center for Biotechnology Information (NCBI) databases, we tried to de novo identify these genes by screening and assembling the raw sequencing data from the NCBI Short Read Archive (SRA). In this preliminary dataset, we found the disruption of the MDA5 gene in nine species: Ciconia boyciana, C. ciconia, C. episcopus, Porzana atra, Gallirallus okinawae, Heliornis fulica, Balearica regulorum, Antigone vipio and Grus nigricollis
Summary
Genome evolution in vertebrates is strongly influenced by their pathogens, including viruses [1,2]. Adaptive changes in host gene sequences are commonly manifested as an increase of the dN/dS ratio (ratio of nonsynonymous over synonymous substitution rates). Diversifying—selection is the hallmark of the evolutionary arms’ race between pathogens and hosts. Other types of adaptive changes include gene gains (e.g., the generation of multigene families by gene duplication) and gene losses [3,4]. Avian viruses include important pathogens with an impact on human health due to cross-species transmission events, best exemplified by the avian influenza viruses (AIV)
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