Origins of Multicellular Life

16 June 2013

Interview with

Rosie Alegado, UC Berkeley.

How did multicellular life evolve?  Ancient ancestors of ours, the choanoflagellates, might give us a clue. Chris Smith spoke with UC Berkeley scientist Rosie Alegado...

eLife Logo Rosie -   We study choanoflagellates which are the closest unicellular relatives to animals.  They look like little sperms with skirts.  They have an ovoid or spherical body with a single flagellum surrounded by a little collar filled with actin.  What they do with their little collar is create water currents that cause bacteria to brush up against their collar so that then they could eat them.

There are several different cell types that we can observe in culture when we grow these choanoflagellates.  One of the most striking are these little bulbs of cells that we call rosette colonies.  The reason why they're very striking is because they look a lot like the morula stage which is one of the very first stages of an animal embryo.  Because choanoflagellates are the closest unicellular relatives to animals, we wondered what might regulate their formation and their development.

Chris -   So, when you say the morula stage, this is them getting together to form a multicellular or at least an organism with more than one cell linked to it.

Rosie -   Correct and I think it's really important to distinguish how they form and they're not formed by individual cells coming together.  So, it's not by aggregating together.  They form from a single founder cell that after cell division, remains together.  That's also very important because that's the same mechanism by which animal development occurs.

Chris -   So, do you think then that what this organism is doing lies upstream of how when an egg begins to grow and the cells come from one founder cell to form the trillion or so cells that make a human for example.  Is it a similar sort of mechanism here?  So, if we understand how it works, it sort of informs how multicellular organisms like us might be doing what they do.

Rosie -   So, we think that that's a very provocative possibility and certainly, that may be the case.  At this point in time, we don't know.  The reason we don't know is because there are about 125 different known species of choanoflagellates, but we don't know if they form colonies in the exact same way.  That's important because if they're all the same then that would indicate that the ancestor of all the choanoflagellates also form colonies in the same way.  If they did, that would provide stronger evidence that this form of multicellular development might inform us about animal development such as embryonic development.

Chris -   So, what triggers them to go into this alternative state where they form cellular derivatives that all remain connected together?

Rosie -   It was actually a complete surprise.  It was really hard to control the cells in culture.  They were very difficult to culture and that was due to the bacteria that was co-isolated with them.  And so, there was an undergrad in the lab and his project was to treat the choanoflagellate cell cultures with antibiotics with the hopes that by taming this culture, making it more easy to propagate, it would be easier for genome sequencing.  The surprising thing that happened was when we treated them with antibiotics.  All of the rosette colonies have disappeared.  And so, you can imagine two possibilities.  One is that the antibiotics directly affect the choanoflagellates in some way, but the other more tempting hypothesis was that we killed off a bacteria that was important for this developmental transition.  And the second possibility turned out to be the case.

Chris -   And suppose you could test that hypothesis if you could get the organism to return to that rosette state, having had it lost or taken away if you were to put those bacteria back in.

Rosie -   That's right and I have to say, the way that this unfolded was very lucky because most of the bacteria in the world are not easily culturable on plates by lab methods.  And so, even if it were a bacteria that caused it, it's not even sure that we would've been able to grow that bacteria.  So, we did two things.  One was, we took just whole cell environmental bacteria and added it back and that seem to induce a return of the rosette colonies.  And so, we kind of had some idea, "Okay, there's something in here.  Maybe it's something that's secreted by the bacteria.  Maybe it's a metabolite."  But it turns out that we were able to culture 64 different environmental isolates from this culture and then add them back individually and only a single environmental isolate was responsible for inducing this transition.

Chris -   I'm sorry to interrupt.  It wasn't a contact phenomenon then.  Could you do it with conditioning media if you grew the bacteria in some media and collect just the media, no bacteria and put that in?  Was that sufficient to make them form this rosette?

Rosie -   Indeed.  It was sufficient for them to make the rosettes.  And so, that also gave us the idea that perhaps what this molecule was, might be something that was intrinsic to the bacteria, something that they were making.  Not even in response to the choanoflagellates.  That led us to think that maybe it was something that was very key to the bacteria's biology such as something that was released unintentionally and that's what turned out to be the key.  So, it turned out to be a component of the cell envelope.

Chris -   So, why do they form these rosettes in response to this secreted molecule from the bacteria?

Rosie -   That is the million dollar question.  We don't know why the rosettes form.  We do have some choanoflagellates seem to be feeding better when they are organised in this multicellular state as opposed to being a single cell swimming around.  And so, that might be one possibility that there's a feeding advantage.  Certainly, we don't know why a bacteria would put out a signal that says, "Eat me!"  So, what we think might be happening is that the choanoflagellates might just be eavesdropping in on bacteria that are happily growing in.  this might actually be a signal to say, "Hey, this is a good patch of food.  Stay around here.  Divide and make a rosette colony."

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