Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds

The respiratory system is the primary route of infection for many contagious pathogens. Mucociliary clearance of inhaled pathogens is an important innate defense mechanism sustained by the rhythmic movement of epithelial cilia. To counter host defenses, viral pathogens target epithelial cells and cilia. For instance, the influenza virus modulates the expression of WDR93, a central ciliary apparatus C1d projection component. Lineage-specific prevalence of such host defense genes results in differential susceptibility. Our comparative analysis of [~]500 vertebrate genomes supports the widespread conservation of WDR93. However, we identified loss of the WDR93 in landfowl, geese, and other phylogenetically-independent bird species. Notably, species with WDR93 loss have concurrently lost another C1d component, CFAP46, through large segmental deletions. Understanding the consequences of such gene loss may provide insight into their role in host-pathogen interactions and benefit global pathogen surveillance efforts by prioritizing species missing host defense genes and identifying putative zoonotic reservoirs.