The ecology of influenza - role of gene loss in natural disease reservoirs

The CDC defines a reservoir of an infectious agent "as the habitat in which the agent normally lives, grows, and multiplies." When the infectious agent spills over from such a reservoir species into other susceptible species, the pathogen experiences strong selective constraints in the new host. This new environment may then select for a more potent pathogen that can spread in the new host or even across other vertebrate species. The brilliant Robert G Webster describes a lifetime of knowledge he has accumulated on this spill-over process in his talk "Influenza: Lessons learned from Pandemic H1N1" at Columbia University. This talk, now more than a decade old, has some interesting discussion at the end that, in hindsight, now after the covid pandemic looks intriguing. 

The most interesting part of the talk for me is when he talks about birds. First, he mentions that shorebirds (Charadriiformes) such as the Ruddy Turnstone (Arenaria interpres), Semipalmated Sandpiper (Calidris pusilla), Sanderling (Calidris alba), European herring gull (Larus argentatus), laughing gull (Leucophaeus atricilla), and Red knot (Calidris canutus) and waterfowl (Anseriformes) species such as mallard or wild duck (Anas platyrhynchos) and pintail or northern pintail (Anas acuta) are some of the migratory birds that are monitored for influenza in North America. The second time he mentions birds is when he explains the difference between Ducks and Chicken and how the RIG-I gene is lost in chickens. RIG-I is an immune sensor that activates the production of interferon-Beta. A more detailed talk that focuses on the loss of this gene and how the discovery was made is explained by Katherine Magor of the University of Alberta in her talk titled "How ducks survive the flu; the secrets of the reservoir host." 

It has been more than a decade since the paper describing the lack of RIG-I in chicken and "Association of RIG-I with innate immunity of ducks to influenza" has been published. In this decade, it has been established that the "Loss of RIG-I leads to a functional replacement with MDA5 in the Chinese tree shrew". Although a paper (from fish immunologist Chris Secombes) looking at the "Origin and evolution of the RIG-I like RNA helicase gene family" claimed that "Unlike RIG-I, whose presence in chicken and some fish species is uncertain..", it did not conclusively establish the lack of RIG-I in chicken. Limitations in genome assembly quality and availability of large genomic datasets can be blamed for these uncertainties. Notably, the paper by Secombes also investigates the origin of RIG-I and related genes through gene fusion, domain duplication, and deletion and follows in the line of a previous paper titled "Evolution of MDA-5/RIG-I-dependent innate immunity: Independent evolution by domain grafting".

The birth and death of the genes from the terminal complement pathway are surprisingly similar to the history of the RIG-I-like RNA helicase gene family. Domain fusion events are involved in the birth of both gene families at the boundary of invertebrates and vertebrates, both RIG-I and C9 are lost in Galliform birds but are present in Anseriform birds and both are involved in the immune response. Finally, our manuscript dealing with the Birth and Death in the Terminal Complement Pathway is published.