Early Chordate Origin of the Vertebrate Integrin αI Domains

Half of the 18 human integrins alpha subunits have an inserted alpha I domain yet none have been observed in species that have diverged prior to the appearance of the urochordates (ascidians). The urochordate integrin alpha I domains are not human orthologues but paralogues, but orthologues of human alpha I 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 alpha I 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 alpha I domain region, have the hallmarks of collagen-binding integrin alpha I domains, and we show that the corresponding recombinant proteins recognize the collagen GFOGER motifs in a metal dependent manner, unlike the alpha 1I domain of the ascidian C. intestinalis. The presence of a functional collagen receptor integrin alpha I 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.