Cell-cell and cell-matrix adhesions are responsible for the formation, composition, architecture, and function of animal tissues. Not surprisingly, some adhesion molecules are evolutionarily ancient and are among the most highly conserved proteins in multicellular organisms. Sponges, the most primitive multicellular organisms, express certain CAMs and multi-adhesive ECM molecules whose structures are strikingly similar to those of the corresponding human proteins. The evolution of metazoans has depended on the evolution of diverse adhesion molecules with novel properties and functions whose levels of expression differ in different types of cells. Some CAMs and adhesion receptors (e.g., cadherins, integrins, and Ig-superfamily CAMs such as L1CAM) and some ECM components (type IV collagen, laminin, nidogen/entactin, and perlecan-like proteoglycans) are highly conserved because they play crucial roles in many different organisms, whereas other adhesion molecules are less conserved. Fruit flies, for example, do not have certain types of collagen or the ECM protein fibronectin, which play important roles in mammals. A common feature of adhesive proteins is repeating, nearly identical domains (sometimes called repeats) that form very large proteins. The overall length of these molecules, combined with their ability to bind numerous ligands via distinct functional domains, probably played a role in their evolution.
The diversity of adhesion molecules arises in large part from two phenomena that can generate the numerous closely related proteins, called isoforms, that constitute a protein family. In some cases, the different members of a protein family are encoded by multiple genes that arose from a common ancestor by gene duplication and divergent evolution (see the human β-like globin gene cluster in Chapter 8). In other cases, a single gene produces an RNA transcript that can undergo alternative splicing to yield multiple mRNAs, each encoding a distinct protein isoform (see Figure 8-3 and Section 10.2). Both phenomena contribute to the diversity of some protein families, such as the cadherins. Particular isoforms of an adhesive protein are often expressed in some cell types and tissues, but not others.