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 defence mechanism sustained by the rhythmic movement of epithelial cilia. To counter host defences, viral pathogens target epithelial cells and cilia. For instance, the avian influenza virus that targets ciliated cells modulates the expression of WDR93, a central ciliary apparatus C1d projection component. Lineage-specific prevalence of such host defence genes results in differential susceptibility. In this study, the comparative analysis of approximately 500 vertebrate genomes from seven taxonomic classes spanning 73 orders confirms the widespread conservation of WDR93 across these different vertebrate groups. However, we established loss of the WDR93 in landfowl, geese and other phylogenetically independent bird species due to gene-disrupting changes. The lack of WDR93 transcripts in species with gene loss in contrast to its expression in species with an intact gene confirms gene loss. 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 defence genes and identifying putative zoonotic reservoirs.