Identification and evolutionary analysis of insect fibrillin with their closely related family proteins

Fibrillins constitute a class of extracellular matrix proteins, and the C-terminal peptide of vertebrate fibrillin members has been identified as a hormone that regulates glucose metabolism. Their evolutionary history has attracted increasing attention recently as the hormonal roles seemingly originated in invertebrates. However, the evolution of fibrillin homologs in invertebrates such as insects, remains poorly understood. In this study, 373 annotated fibrillin sequences (including fibrillin-1, fibrillin-2, and fibrillin-3) from 181 species, 126 genera, 65 families, and 12 insect orders were retrieved and analyzed. Multidimensional analysis of phylogenesis, sequence features, conserved motifs, functional domains, and three-dimensional structures was performed on these sequences to elucidate their evolutionary relationships. Phylogenetic analysis categorized all annotated insects fibrillin sequences into three distinct clades. Among them, only the fibrillin-2 annotated members exhibit clear homology to the vertebrate fibrillin family, having diverged early from a putative ancestral protein together with the other two fibrillin annotated groups. Analysis of cysteine ratio, motif, domain composition, and furin cleavage site also revealed that only insect fibrillin-2 annotated homologs share highly similar sequence and structural features with vertebrate fibrillins. By contrast, the other two insect fibrillin annotated members are more divergent from the canonical fibrillin. Combined analyses of sequence conservation, phylogeny, domain analysis, and three-dimensional structural comparisons demonstrates that insect annotated fibrillin-1 proteins are more closely related to vertebrate fibulin than to canonical fibrillins, whereas insect annotated fibrillin-3 proteins may represent an uncharacterized insect-specific protein family associated with cell adhesion. These two groups are closely related to proteins of fibrillin family and have been misannotated in public database.