Molecular evolution of integrins: genes encoding integrin beta subunits from a coral and a sponge

Abstract

The integrin family of cell surface receptors is strongly conserved in higher animals, but the evolutionary history of integrins is obscure. We have identified and sequenced cDNAs encoding integrin beta subunits from a coral (phylum Cnidaria) and a sponge (Porifera), indicating that these proteins existed in the earliest stages of metazoan evolution. The coral betaCn1 and, especially, the sponge betaPo1 sequences are the most divergent of the "beta1-class" integrins and share a number of features not found in any other vertebrate or invertebrate integrins. Perhaps the greatest difference from other beta subunits is found in the third and fourth repeats of the cysteine-rich stalk, where the generally conserved spacings between cysteines are highly variable, but not similar, in betaCn1 and betaPo1. Alternatively spliced cDNAs, containing a stop codon about midway through the full-length translated sequence, were isolated from the sponge library. These cDNAs appear to define a boundary between functional domains, as they would encode a protein that includes the globular ligand-binding head but would be missing the stalk, transmembrane, and cytoplasmic domains. These and other sequence comparisons with vertebrate integrins are discussed with respect to models of integrin structure and function.

Figure 2

Expected β_Po1 fragment generated by alternative RNA splicing. The protein would be expected to consist of the β ligand-binding domain (solid shading) without the stalk and cytoplasmic regions (light shading).

Figure 1

Alignment of amino acid sequences of coral β_Cn1 and sponge β_Po1 with β₁-like integrin subunits. Numbers above the sequences indicate the 56 conserved cysteines, and numbers to the right of each block denote the position in the matrix. Residues mentioned in the text are indicated by ∗ below the block. The amino acid change and stop codon in the alternatively spliced sponge cDNAs are indicated below the block at position 521. The transmembrane domain is the largely green region around position 920. No attempt was made to align the signal sequences before the first conserved cysteine. The color scheme used to indicate amino acid similarity is: yellow, proline; red, cysteine; magenta, alanine, glycine, serine, and threonine; blue, asparagine, histidine, phenylalanine, tryptophan, and tyrosine; cyan, arginine and lysine; green, isoleucine, leucine, methionine, and valine, and black, aspartic acid, glutamic acid, and glutamine.

Figure 3

Tree showing relationships of β subunit sequences, generated using paup heuristic parsimony algorithm. The tree is unrooted; see text for details.