Molecular Phylogeny and Evolution of the Coronin Gene Family

Abstract

The coronin gene family comprises seven vertebrate paralogs and at least five unclassified subfamilies in nonvertebrate metazoa, fungi and protozoa, but no representatives in plants or distant protists. All known members exhibit elevated structural conservation in two unique domains of unknown function (DUF1899 and DUF1900) interspaced by three canonical WD40 domains (plus additional pseudo domains) that form part of a 7-bladed β-propeller scaffold, plus a C-terminal variable “coiled coil domain” responsible for oligomerization. Phylogenetic analysis of the N-terminal conserved region in known members (i.e.420 aa in 250 taxa) established the origin of the founding monomeric unit and a dimeric paralog in unicellular eukaryotes. The monomeric ancestor duplicated to two distinct lineages in basal metazoa and later propagated during the whole genome duplications in primitive chordates 450–550 million years ago to form six vertebrate-specific genes. The delineation of 12 subfamily clades in distinct phyla provided a rational basis for proposing a simplified, universal nomenclature for the coronin family in accordance with evolutionary history, structural relationships and functional divergence.

Comparative genomic analysis of coronin subfamily locus maps and gene organization provided corroboratory evidence for their chromosomal dispersal and structural relatedness. Statistical analysis of evolutionary sequence conservation by profile hidden Markov models (pHMM) and the prediction of Specificity Determining Positions (SDPpred) helped to characterize coronin domains by highlighting structurally conserved sites relevant to coronin function and subfamily divergence. The incorporation of such evolutionary information into 3D models facilitated the distinction between candidate sites with a structural role versus those implicated in dynamic, actin-related cytoskeletal interactions. A highly conserved “KGD” motif identified in the coronin DUF1900 domain has been observed in other actin-binding proteins such as annexins and is a potential ligand for integrins and C2 domains known to be associated with structural and signalling roles in the membrane cytoskeleton. Molecular evolution studies provide a comprehensive overview of the structural history of the coronin gene family and a systematic methodology to gain deeper insight into the function(s) of individual members.