Zip up and stick together...

… could have been a really cheesy line in an action movie. It’s also what cells in multicellular metazoans do! A little single-celled creature contains some clues about the origins of all this stickiness.

You might not realize it, but being multicellular is quite a feat! Your cells need to divide and grow at exactly the right moment and every cell needs to be told how it has to behave and what it should do. But first and foremost: your cells have to stick together. It’s how we define multicellular organisms. At some point in the evolution of metazoans, our single celled ancestor acquired the capability to team up with its brothers and sisters. This union was probably temporary at first, like the many fungi or protists that form colonies, and became permanent only much later. It’s our closest unicellular nephew that contain traces of the origin of stickiness.

A model of a cadherin zipper. The orange and purple cadherins belong to different cells that stick together thanks to the zipper. Figure from Shapiro et. al, 1995.

Animal cells stick together differently than fungal and plant cells do, using proteins called cadherins, amongst others. These cadherins are the glue between your cells. Scientists have developed different models as to how they exactly do this, including a zipper-model where cadherin proteins from opposing cells alternatively associate which each other, like in the figure above.

Surely, having such proteins would only be useful if you’ve got multiple cells to string together? Apparently not. The freedom-loving choanoflaggelates, the closest unicellular nephews of animals, have been shown to have cadherins of their own, in a 2008 Science paper by Monika Abedian. The main star of this paper is the tiny Monosiga brevicollis, which is shown in funky red and green below. Monosiga is not known to form cell-cell contacts, so discovering cadherins in these creatures was quite a surprise!

Monosiga brevicollis, one of our closest single-celled relatives. Their tail-like flagellum is used as a propeller to move through water, as they hunt for bacteria. Source.

The 23 cadherins that were found in Monosiga contained other domains which shed some light on the evolution of other ‘metazoan’ systems. One such domain is the SH2 domain, which binds proteins that contain phosphorylated tyrosine residues. Apparently tyrosine phosphorylation predates the metazoan origin by a good deal! Other domains that were found include immunoglobulin (Ig), EGF, LamG and other transmembrane domains. It appears that a lot of these domains have been coopted in metazoans for different purposes.

Given what I just told you about the sticky cadherins, you might expect that this little single-celled creature has fewer cadherin genes than metazoans do. They don’t have to stick all these different cells together after all. But the humble Monosiga contains a respectable 23 cadherin genes! This is 0.25% of all Monosiga genes, comfortably falling between the 0.12% of fruit flies and 0.39% of mice!

Why would Monosiga bother carrying these genes around if it’s not going to use them for sticking around? When Abedin and King tracked where the cadherin genes were going, they found that they localized to the feeding collar of the protist. The choanoflaggelates use these collars for filtering bacteria from the water. Since it is known that metazoan cadherins are sometimes exploited by pathogenic bacteria to gain entry to the cell, Abedin and King came up with a pretty awesome hypothesis.

They sketch the scenario that cadherins initially evolved to recognize or catch bacterial prey in the common ancestor of choanoflaggelates and metazoans. Later, the stickiness of cadherins made them pretty good cell adhesion molecules, so they were coopted for that role. That nasty germs now use the cadherins for which they originally evolved is pretty ironic, but understandable knowing where cadherins came from!

It seems that the transition to multicellularity involved a lot of mixing and matching of existing parts. Re-purposing molecules and systems seems to be life’s rule rather than the exception. It all shows that evolution doesn’t follow plans. It tinkers. Only sometimes does it stumble upon unlikely but wonderful solutions.

Where did all the tyrosine go?
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