The invention of multicellularity

Multicellular yeast cluster. Photo courtesy of William Ratcliff.

In January, William Ratcliff and his colleagues from the University of Minnesota caused quite a stir with their study on the experimental evolution of multicellularity in yeast, published in PNAS. Many media covered the story, including the New York Times, Wired and Scientific American. Briefly, what they did was using artificial selection on unicellular yeast (the baker's yeast Saccharomyces cerevisiae) in order to create an obligate multicellular organism after many generations of selection. What is impressive is that it worked pretty well in all their different test cultures!

Multicellularity was invented several times during the history of life (Rokas, 2008), but since it happened a long time ago it is difficult to reconstruct the exact sequence of events. Experimentation on today's unicellular organisms, however, allows researchers to test mechanisms (and associated mutations) that could lead to a multicellular lifestyle. Of course, this cannot decide for good how the phenomenon occurred many millions years ago – which is not at all the author's claim – but this can prove that such mechanisms can occur, given that an appropriate selection pressure is present.



In the PNAS paper, the authors used gravity to play the role of selective agent, and therefore favor aggregates of yeast against single yeast cells. As Ratcliff et al. note, sedimentation is not necessarily a common selection factor in nature, but it is very convenient for the purpose of the experiment. [I can think of one example of gravity selection, albeit not in a natural system, it is the selection of flocculating bacteria in activated sludge in waste water treatment plants.] Many generations are necessary before a difference is seen, but the authors observe that it always leads to the apparition of a multicellular "snowflake" phenotype. This phenotype is stable and yeast reproduce as a multicellular organism. 

Before they performed their experiment, the authors postulated that multicellular yeast could arise by two mechanisms: aggregation of different single cells or what they call "postdivision adhesion". [It immediately reminded me of our own study on the formation of bacterial clusters on the leaf surface, although the context is totally different. It's just that mechanistically you don't have so many options to create clusters of cells!] What they also discovered is that the evolved clustered yeast develops apoptosis mechanism in order to split in smaller ones and hence reproduce (see the picture on top, apoptotic cells are stained with a green fluorescent dye and these cells correspond to weaker points where the structure is susceptible to break).

In the movie below, you can see how these "snowflake" clusters grow and multiply!

The main conclusions of the paper are as follows:

• Transition from unicellularity to multicellularity can happen pretty quickly.
• In all the different test cultures, only "postdivision adhesion" is observed, never aggregation.
• Cell "division of labor" is developed: apoptotic cells help the clusters to break apart and reproduce.

But if it is so simple to produce multicellularity, why did it take so long (hundreds of millions of years) to produce multicellular eucaryotes? But maybe I'm mistaken here... I guess the first metazoans had to be quite complex to appear in the fossil record, so information on the first small multicellular organisms might be limited. The authors also suggest that the evolution of aggregative-clustering was not observed because it was handicapped by within-group conflict, but I'm not really convinced by this explanation. It seems to me that it is simply more likely that mutations will favor postdivision adhesion rather than aggregation. Anyway this is a very nice work and certainly worth reading! 


To conclude, here's a  a very funny anecdote that Carl Zimmer reports in his NYT piece, to explain the birth of the project:
During a coffee break, Ratcliff and his adviser, Michael Travisano, were wondering what would be the coolest experiment they could do in the lab. Looking for the origins of life? Probably too hard. So what would be the second coolest thing? Well, what about evolution of multicellularity! [Coffee is the scientist's best friend and a great provider of ideas...]

Now I'm curious to know what mutations are responsible for the evolution of these multicellular clusters, and if they are the same in all test cultures. No doubt it's under way in the micropop lab, so there's probably more to come in the near future! 

Note: I purposely don't discuss here the invention of multicellularity in bacteria. There is a lot to say and I keep it for another post!

References:

• Ratcliff W. C., Ford Denison R., Borrello M. and M. Travisano (2012). Experimental evolution of multicellularity. PNAS 109, pp. 1595-1600. 
• Rokas A. (2008). The origins of multicellularity and the early history of the genetic toolkit for animal development. Annu.Rev.Genet. 42, pp.235-251.