Early chordate origin of the vertebrate integrin αI domains.

Half of the 18 human integrins α subunits have an inserted αI domain yet none have been observed in species that have diverged prior to the appearance of the urochordates (ascidians). The urochordate integrin αI domains are not human orthologues but paralogues, but orthologues of human αI 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 αI 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 αI domain region, have the hallmarks of collagen-binding integrin αI domains, and we show that the corresponding recombinant proteins recognize the collagen GFOGER motifs in a metal dependent manner, unlike the α1I domain of the ascidian C. intestinalis. The presence of a functional collagen receptor integrin αI domain supports the origin of orthologues of the human integrins with αI domains prior to the earliest diverging extant vertebrates, a domain that has been conserved and diversified throughout the vertebrate lineage.

Evolution of integrin I domains.

In humans, an ~200-residue "inserted" I domain, a von Willebrand factor A domain (vWFA), buds out from the ß-propeller domain in 9 of 18 integrin α subunits. The vWFA domain is not unique to the α subunit as it is an integral part of all integrin ß subunits and many other proteins. The ßI domain has always been a component of integrins but the αI domain makes its appearance relatively late, in early chordates, since it is found in tunicates and later diverging species. The tunicate αI domains are distinct from the human collagen and leukocyte recognizing integrin α subunits, but fragments of integrins from agnathastomes suggest that the human-type αI domains arose in an ancestor of the very first vertebrate species. The rise of integrins with αI domains parallels the enormous changes in body plan and systemic development of the chordate line that began some 550 million or more years ago.