In humans, an ~200-residue "inserted" I domain, a von Willebrand factor A domain (vWFA), buds out from the β-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 β subunits and many other proteins. The βI 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.