If you wanted to channel a single-celled organism toward the evolution of a metazoan state, various themes would have to emerge, including the ability of cells to connect to each other, communicate to each other from a distance, and the ability to recognize self. In the past, I have been filling in some of the details to front-load cell connections (see here and here) and signaling (the tyrosine kinases, which we’ll be getting back to). Today, let me touch on another neat example of intercellular communication.

A common signaling pathway that is very important in metazoan development involves the protein hedgehog, which acts as a morphogen (a nice review can be found here).

In animals, the protein hedgehog is composed of two domains. There is the N-terminal signaling domain that is secreted by cells and functions as the morphogen. And there is a C-terminal Hint domain, that is an auto-catalytic protein domain that cuts itself away from the signaling domain to facilitate the processing of the signaling domain.

What I want you to do now is consider the following figure from a recent paper by Shalchian-Tabrizi et al.

At the top, you’ll notice the arrangement I just mentioned (signaling domain in brown and Hint domain in blue (with its cleavage site in green)). The next arrangement is from Nematostella, which is a cnidarian - same as humans.

Next, consider the sponge Amphimedonm. Here, the two domains exist, but are found on separate genes. In other words, the information for making the cnidarian/human version of hedgehog is present and it is simply up to genetic recombination (under the guidance of evolution genes) to paste the two domains together.

Now look at the section marked Choanozoa, which represent the single-celled lineages among the opisthokonts. Monosiga is a choanoflagellate and it too possesses both the signaling domain and the Hint domain.

Right there, in a single-celled organism, is the information needed to put together one of the most important morphogens needed to sculpt everything from the jellyfish to the fish to the reptile to the human. Just as we would expect if metazoan life was front-loaded to evolve.