Expansion of amphibian intronless interferons revises the paradigm for interferon evolution and functional diversity

Abstract

Interferons (IFNs) are key cytokines identified in vertebrates and evolutionary dominance of intronless IFN genes in amniotes is a signature event in IFN evolution. For the first time, we show that the emergence and expansion of intronless IFN genes is evident in amphibians, shown by 24–37 intronless IFN genes in each frog species. Amphibian IFNs represent a molecular complex more complicated than those in other vertebrate species, which revises the established model of IFN evolution to facilitate re-inspection of IFN molecular and functional diversity. We identified these intronless amphibian IFNs and their intron-containing progenitors, and functionally characterized constitutive and inductive expression and antimicrobial roles in infections caused by zoonotic pathogens, such as influenza viruses and Listeria monocytogenes. Amphibians, therefore, may serve as overlooked vectors/hosts for zoonotic pathogens, and the amphibian IFN system provides a model to study IFN evolution in molecular and functional diversity in coping with dramatic environmental changes during terrestrial adaption.

The Peculiar Characteristics of Fish Type I Interferons

“…A diverse array of type I IFN genes should constitute a beneficial trait, likely through functional specialization of the multiple copies or ability to escape virus inhibition (see below, Part 2). This view is also supported by the recent discovery of expanded intronless type I (and type III) IFN in frogs, besides type I and type III IFN genes with introns as found in fish [13,32]. Thus far, no intronless type I IFN genes have been found in fish, and all type I IFN genes identified in the coelacanth genome have introns [33].…”

Intronless and intron-containing type I IFN genes coexist in amphibian Xenopus tropicalis : Insights into the origin and evolution of type I IFNs in vertebrates

“…considered that the scenario might be the case at least in X. tropicalis, and probably in the amphibian lineage, as intronless and intron-containing type I IFNs have been identified in a similar amphibian model species, X. laevis (Sang et al, 2016).…”

“…While this manuscript was in preparation and review, intronless type I IFNs were identified from another amphibian model species X. laevis by Blecha and coworkers, and inductive expression and antimicrobial roles of intronless type I IFNs in X. laevis against influenza viruses and a pathogenic bacterium Listeria monocytogenes were also examined (Sang et al, 2016). The discovery of intronless type I IFNs both in X. laevis and X. tropicalis implies that intronless and intron-containing type I IFN genes may coexist commonly in the Xenopus, and probably in the amphibian lineage.…”

Contribution of type III interferons to antiviral immunity: location, location, location

“…Interferons (IFNs) 3 represent a group of cytokines that are able to induce resistance to virus infections in treated cells. Most vertebrates possess three types (or families) of IFNs, based on similarities in gene and protein sequences and structures, receptor utilization, and biological functions, which are shared among the members of each IFN type but are distinct between the three IFN types.…”