Front-loading and Epithelial Tissue

Your body is composed of four basic tissues: epithelial, connective, muscle, and nervous. Epithelial tissue is essentially a sheet of cells that is used to cover structures and line cavities and vessels. For example, your digestive and respiratory tracts are lined with epithelial tissue and the very surface of your skin is epithelial tissue. Furthermore, epithelial tissue is used to form all the glands in your body. Could unicellular creatures encode all, or most, of the machinery that would be needed to form such tissues?

To form epithelial tissue, we are going to need a way to connect individual cells into a sheet. One commonly used strategy is to form adherens junctions. Below is a figure of an adherens junction:


The blue sheets represent the membranes of two adjacent cells (see the figure in the upper left corner). The two membranes are held together by membrane proteins known as cadherins (the green candy canes). In essence, this is life’s version of Velcro, as a sheet of cadherins on one cell link up with a cadherin sheet on the other cell. Yet it is more sophisticated than this. First, cadherin interactions are modulated by calcium, as the removal of calcium prevents the cells from connecting to each other. Second, the cytoplasmic face of the cadherin interacts with the cell’s cytoskeleton. In essence, this means that a sheet of cells is effectively connected through their respective cytoskeletons, such that a tissue is more than a clump of cells. Third, cadherins can function both as a ligand and a receptor, meaning they can serve as players in transmitting signals from one cell to the next.

Let’s look more closely at the cytoplasmic components:

As you can see, the cadherins are connected to the cytoskeleton (microfilaments composed of actin) though a set of linker proteins: alpha-catenin, beta-catenin, alpha-actinin, and vinculin. So here is the question. Is it plausible that this system, needed to form adherens junctions, was front-loaded in unicellular organisms? If so, to what extent was it front-loaded?

Choanoflagellates are single-celled organisms thought to be most closely related to animals. The genome of Monosiga brevicollis, one species of choanoflagellate, has been recently sequenced [1] and found to contain many genes previously thought to be restricted to animals. Included in this list are 23 genes for cadherins. This is very encouraging from the perspective of front-loading. Yet these cadherin genes lack the cytoplasmic domain, suggesting they are not connected to the cytoskeleton. In fact, it does not appear that choanoflagellates code for these various linker proteins either. Thus, this particular species has only the extracellular domains of the cadherins and the actin cytoskeleton (universal among eukarya).

Yet we need to remember that Monosiga brevicollis is not some primitive protozoan, but is a species that has been evolving alongside animals for hundreds of millions of years. It is thus possible that the last common ancestor of choanoflagellates and animals did possess most of the components to form an adherens junction and that the choanoflagellate lineage has since lost these genes.

There are two lines of support for this hypothesis. First, with the sequencing of more metazoan genomes, it is becoming clear that gene loss has played a large role in metazoan evolution. For example, when the genome for a sea anemone was sequenced, it was determined that the ”sea anemone genome is complex, with a gene repertoire, exon-intron structure, and large-scale gene linkage more similar to vertebrates than to flies or nematodes, implying that the genome of the eumetazoan ancestor was similarly complex.” [2] Thus, the idea that animal genomes are more reflective of the ancestral state than choanoflagellate genomes would fit within this trend.

Second, what if we survey for adherens junction genes in various other protozoa, more distantly related to animals than choanoflagellates? While it is important to keep in mind that most of the planet’s protozoans have not studied and only a handful of protozoan genomes have been sequenced, the information we do possess is quite encouraging. For example, a “beta-catenin homologue with both cytoskeletal and signal transduction roles” has been previously discovered in the amoebae, Dictyostelium discoideum. [3] Vinculin has been discovered in Giardia [4] and perhaps Amoeba proteus. [5] And alpha-actinin has been discovered in Entamoeba histolytica [6] and Trichomonas vaginalis . [7]

It thus appears that most of the components needed to form adherens junctions, the cadherins, actins, beta-catenins, vinculins, and alpha-actinins, all existed prior to the appearance of animals, epithelial tissue, and adherens junctions. It is possible that all these genes were present in the ancestral protozoan organism that then spawned both choanoflagellates and metazoans.


1. King N, Westbrook MJ, Young SL, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsten U, Isogai Y, Letunic I, Marr M, Pincus D, Putnam N, Rokas A, Wright KJ, Zuzow R, Dirks W, Good M, Goodstein D, Lemons D, Li W, Lyons JB, Morris A, Nichols S, Richter DJ, Salamov A, Sequencing JG, Bork P, Lim WA, Manning G, Miller WT, McGinnis W, Shapiro H, Tjian R, Grigoriev IV, Rokhsar D. 2008. The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451(7180):783-788.


3. Coates JC, Grimson MJ, Williams RS, Bergman W, Blanton RL, Harwood AJ. 2002. Loss of the beta-catenin homologue aardvark causes ectopic stalk formation in Dictyostelium. Mech Dev. 116:117-27.

4. Narcisi EM, Paulin JJ, Fechheimer M. 1994. Presence and localization of vinculin in Giardia. J Parasitol. 80:468-73.

5. Brix K, Reinecke A, Stockem W. 1990. Dynamics of the cytoskeleton in Amoeba proteus. III. Influence of microinjected antibodies on the organization and function of the microfilament system. Eur J Cell Biol. 51:279-84.

6. Virel A, Backman L. 2006, Characterization of Entamoeba histolytica alpha-actinin. Mol Biochem Parasitol. 145:11-7.

7. Bricheux G, Coffe G, Pradel N, Brugerolle G. 1998. Evidence for an uncommon alpha-actinin protein in Trichomonas vaginalis. Mol Biochem Parasitol. 95:241-9.

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