Architecture of distal tips of motile cilia is shaped by the pseudoenzyme Jhc1 in non-mammalian vertebrates.

Abstract

Motile cilia are evolutionarily conserved organelles performing essential roles in development and tissue homeostasis. Unlike the core scaffold, the distal regions remain relatively less explored and display great diversity across species. Here, we describe a previously uncharacterized ciliary protein Jhc1 (just the head of cilia 1, Loc108698169), localizing at the extreme distal tip of multiciliated cell (MCC) cilia and encoded only in the genomes of non-mammalian vertebrates. Jhc1 is essential for normal cilia structure and function in Xenopus, and this activity is conserved in Jhc1 from reptiles and fish. Phylogenetic analysis and structure modeling suggest that Jhc1 arose by duplication and neofunctionalization of thiamine triphosphatase, and the residues crucial for that enzyme's function have been lost and replaced by residues essential for ciliary localization. These data provide insights into the molecular mechanisms underlying the broad diversification of the structures at the tip of motile cilia during vertebrate evolution.