The principle of common descent in evolutionary theory means that all living organisms are related to each other in a genealogical sense. In other words, many of the similarities between different organisms exist because they were inherited from a common ancestor with those features. Since inherited traits are encoded in the DNA of the organisms, comparisons of their genes is a way to infer descent from a common ancestor.
One of the similarities among all metazoans is their multicellularity, which requires proteins that enable cells to adhere and communicate. A number of cell adhesion and cell-cell signaling proteins do this in multicellular organisms, but only such proteins that exist in all (or nearly all) modern metazoans, but not in any other multicellular organisms such as fungi and plants, should have been present in the last common ancestor (LCA) of metazoans. The cadherin family of proteins apparently meets this criteria.Cadherins have also been found in the choanoflagellates, which are unicellular and sometimes colony-forming organisms. Each cell has a single flagellum surrounded by a collar (choano comes from the Greek word for collar) of microvilli that it uses to swim and capture bacterial prey. As the flagellum beats, it draws water through the collar’s microvilli, which filter out bacteria and other tiny food particles. Choanoflagellates are nearly indistinguishable, in terms of shape and function, from the “collar cells” (choanocytes) of sponges, the simplest metazoans. The beating flagella of choanocytes generate a current that draws water and food particles through the body of the sponge, and their microvilli filter out food particles. Henry James-Clark first recognized this remarkable similarity over 130 years ago, which eventually led to the hypothesis that sponges, and, by implication, other animals, evolved from choanoflagellate-like ancestors.
To investigate this possibility, Abedin and King first examined the published genomes of a choanoflagellate, Monosiga brevicollis, and four diverse animals to identify cadherin genes in each. Surprisingly, despite the lack of obvious cell adhesion in M. brevicollis, its number of putative cadherin genes (23) is greater than the number of recognized cadherin genes in the fruitfly Drosophila melanogaster (17). Of the other animals they looked at, the mouse Mus musculus has the most cadherin genes (127), followed by the sea anemone Nematostella vectensis (46), and the sea squirt Ciona intestinalis (32). When compared as a percentage of the total number of genes in each genome, cadherins are more common in M. brevicollis than in any of the four metazoans except M. musculus.The cadherin repeat is a repeating domain (functional subunit of a protein) found in all cadherin proteins, which enables them to adhere to each other and which depends on calcium ions (Ca+2) to function (cadherins are named after it). A cadherin protein typically consists of an extracellular region, a single membrane-spanning region, and a cytoplasmic region. The cadherin repeat is found in the extracellular region; surprisingly, in comparing the five organisms, Abedin and King discovered that the average number of extracellular cadherin repeats (ECs) in M. brevicollis is highest (14.7), while the average in M. musculus is lowest (5.2).
In the extracellular and cytoplasmic regions of different cadherin proteins, other distinctive domains can be found. The extracellular domains EGF and LamG are shared by M. Brevicollis, N. vectensis, and M. musculus, while the extracellular domains N-hh and IG and the cytoplasmic domain SH2 are shared by M. brevicollis and N. vectensis. This suggests that these domains were present in the LCA of choanoflagellates and metazoans. A cytoplasmic domain called the classic cytoplasmic domain (CCD) is responsible for the ability of classic cadherin proteins (defined as those involved in cell-cell adherens junctions) to anchor, with the help of catenins, to the actin cytoskeleton. As a result, the actin cytoskeleton of one cell can be linked to the cadherins in the plasma membrane, which in turn attach through their extracellular regions to the cadherins in the neighboring cell membranes. However, since CCDs are found in N. vectensis and M. musculus but not in M. brevicollis, the CCD-containing cadherins probably evolved after the origin of the metazoans.
Given that Monosiga brevicollis leads a unicellular lifestyle and is not known to form cell-cell contacts, what are its putative cadherins doing? In an effort to answer this question, Abedin and King determined the locations in choanoflagellate cells of two nearly identical cadherin proteins, MBCDH1 and MBCDH2. Both of them resemble the inferred ancestral cadherin in having SH2 domains but not CCDs. The locations of polymerized actin in the cells were also determined. The experiments showed that actin, MBCDH1, and MBCDH2 proteins were localized together around the base of the choanoflagellate cell, where the choanoflagellate attaches to surfaces, and especially around the microvilli of the collar, where bacteria are captured and ingested. This implies that the associations between cadherins and actin filaments was present in the LCA of choanoflagellates and metazoans. But why?
The localization of these ancient cadherin proteins suggests that perhaps the choanoflagellate/metazoan LCA used them to bind and eat bacteria, while the multicellular metazoans adopted these proteins for gluing their cells together. Abedin and King support this hypothesis by pointing out that some pathogenic bacteria today bind to the extracellular region of metazoan cadherins, taking advantage of them to help invade the host cell. “Indeed, the transition to multicellularity likely rested on the co-option of diverse transmembrane and secreted proteins to new functions in intercellular signaling and adhesion,” they conclude in their report.
- Abedin, M., King, N. (2008). The Premetazoan Ancestry of Cadherins. Science, 319(5865), 946-948. DOI: 10.1126/science.1151084
- King, N. (2004). The Unicellular Ancestry of Animal Development. Developmental Cell, 7(3), 313-325. DOI: 10.1016/j.devcel.2004.08.010
- Snell, E. (2001). Hsp70 sequences indicate that choanoflagellates are closely related to animals. Current Biology, 11(12), 967-970. DOI: 10.1016/S0960-9822(01)00275-5
- University of California – Berkeley. “Genome Of Marine Organism Tells Of Humans’ Unicellular Ancestors.” ScienceDaily 20 February 2008. 31 March 2008 .