Ancient origin of the integrin-mediated adhesion and signaling machinery

Abstract

The evolution of animals (metazoans) from their unicellular ancestors required the emergence of novel mechanisms for cell adhesion and cell-cell communication. One of the most important cell adhesion mechanisms for metazoan development is integrin-mediated adhesion and signaling. The integrin adhesion complex mediates critical interactions between cells and the extracellular matrix, modulating several aspects of cell physiology. To date this machinery has been considered strictly metazoan specific. Here we report the results of a comparative genomic analysis of the integrin adhesion machinery, using genomic data from several unicellular relatives of Metazoa and Fungi. Unexpectedly, we found that core components of the integrin adhesion complex are encoded in the genome of the apusozoan protist Amastigomonas sp., and therefore their origins predate the divergence of Opisthokonta, the clade that includes metazoans and fungi. Furthermore, our analyses suggest that key components of this apparatus have been lost independently in fungi and choanoflagellates. Our data highlight the fact that many of the key genes that had formerly been cited as crucial for metazoan origins have a much earlier origin. This underscores the importance of gene cooption in the unicellular-to-multicellular transition that led to the emergence of the Metazoa.

Fig. 1.

Comparison of the functional domains and amino acid motifs between canonical metazoan and nonmetazoan integrins. (A) Integrin β amino acid motifs and (B) amino acid motifs and schematical alignment of integrin α (, –39). Integrin β is divided into the integrin β extracellular domain (orange), integrin stalk (blue), interaction motif (gray), and cytoplasmic tail (green). The T. erytrhaeum homolog possesses only the integrin β domain. For the MIDAS, ADMIDAS, and LIMB motifs within the integrin β domain, we indicate the canonical metazoan amino acids and their positions within the whole protein. In red are shown nonconserved position and motifs. For the remaining motifs, the number of motifs present is indicated. Integrin α is divided into the three FG-GAP cation binding motifs and the integrin α–β interacting motif after the transmembrane domain. Key amino acids experimentally determined in the α–β interacting motifs are depicted in bold (17).

Fig. 2.

Schematic representation of the eukaryotic tree of life showing the distribution of the different components of the integrin adhesion complex. The number of integrin homologs is shown. A black dot indicates the presence of clear homologs, whereas a hollow dot indicates the presence of putative or degenerate homologs. Absence of a dot indicates that a homolog is lacking in that taxon. The phylogenetic relationships are based in several recent phylogenetic studies (8, 9, 15, 40, 64, 65).

Fig. 3.

Schematic representation of integrin-mediated cell-adhesion and cell-signaling evolution. Left: The canonical metazoan integrin adhesion complex. The colors correspond to the three main steps in the evolution of the integrin adhesion mechanism, as shown in the cladogram. Dots indicate origin, and crosses indicate losses. The branch leading to Amastigomonas sp. is shown dashed, because its phylogenetic position remains unresolved (see main text for discussion).