Early Chordate Origin of the Vertebrate Integrin aI Domains

Half of the 18 human integrins a subunits have an inserted aI domain yet none have been observed in species that have diverged prior to the appearance of the urochordates (ascidians). The urochordate integrin aI domains are not human orthologues but paralogues, but orthologues of human aI domains extend throughout later-diverging vertebrates and are observed in the bony fish with duplicate isoforms. Here, we report evidence for orthologues of human integrins with aI domains in the agnathostomes (jawless vertebrates) and later diverging species. Sequence comparisons, phylogenetic analyses and molecular modeling show that one nearly full-length sequence from lamprey and two additional fragments include the entire integrin aI domain region, have the hallmarks of collagen-binding integrin aI domains, and we show that the corresponding recombinant proteins recognize the collagen GFOGER motifs in a metal dependent manner, unlike the a1I domain of the ascidian C. intestinalis. The presence of a functional collagen receptor integrin aI domain supports the origin of orthologues of the human integrins with aI domains prior to the earliest diverging extant vertebrates, a domain that has been conserved and diversified throughout the vertebrate lineage.