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Where Does Cooperation Come From?

The evolution of mutualism has long been one of life’s big mysteries. Will Harcombe’s lab may have cracked the code.

Will Harcombe Lab

The biological world is filled with “you scratch my back, I’ll scratch yours” relationships in which two organisms each benefit the other at a cost to themselves. It’s easy to see the advantages of such mutualisms once a relationship is up and running — for instance, bees serving as pollen couriers for stuck-in-place plants, while the plants make nectar to keep the bees coming back.  But how do such interactions evolve without one organism first giving at expense to themselves but getting nothing in return?

CBS assistant professor William Harcombe and colleagues just might have the answer. As they reported in the Proceedings of the National Academy of Sciences in October, Harcombe and fellow researchers were able to create conditions that led to the evolution of a mutualistic relationship between two species of bacteria—providing support for a long-standing theory about how such a relationship can take root.

The theory, which has been around since the 1970s or so, goes like this: One species—let’s call it Species A—produces a waste product that is of no benefit to itself. A second organism, Species B, can use the waste product, perhaps as a source of energy or nutrients. Over time, Species B then evolves to produce a substance that helps Species A thrive and so make more of the waste product. Species A then evolves to provide a costly product rather than just waste, because of the added benefits of supporting the now beneficial Species B.

Which all sounds good on paper. But how to prove whether it can actually happen in real life? Harcombe stumbled onto a system to test this theory by accident. He was trying to study competition between two bacterial species, Escherichia coli and Salmonella enterica, but the two seemed to be coexisting rather than competing.

It turned out that E. coli was giving off a waste product that Salmonella was using as food. As the bacteria reproduced, eventually a mutation arose in the Salmonella that allowed it to produce methionine, a molecule that benefited E. coli. That mutation was favored in Salmonella growing near E. coli, since it helped E. coli grow and thus produce more food for Salmonella —providing proof of principle for the first half of the mutualism-evolution theory.

“Once we realized there was this waste consumption going on, that had been proposed as a stepping stone to mutualism, my question was: ‘Can we get it all the way up to where both species were paying a cost?’” Harcombe recalls.

To find out, he grew the two species together on multiple petri dishes for hundreds of generations. Eventually, in many of the communities, they started to see something new: a strange dark-colored colony.

It turned out to be E. coli that had evolved a new twist: the ability to secrete a sugar that Salmonella could use to make more Salmonella. Essentially, the second half of a mutualism had evolved before their eyes.

Harcombe enlisted postdoctoral fellow Jeremy Chacón to create computer simulations to try to explain the observations—in particular, the observation that the mutant bacteria and those that didn’t produce the sugar were able to co-exist on the same petri dish. Graduate student Beth Adamowicz tested the computer models in the lab to see which most closely explained observations.

“The evolution was pretty straightforward. The challenge was figuring out what had happened and why,” Harcombe says.

It’s understandably quite satisfying to have provided proof of principle for a longstanding theory. But Harcombe notes that the research also offers valuable new insights for managing microbial communities in the environment, in manufacturing, and even in our own bodies.

“There is a lot of excitement around trying to harvest the power of microbial communities for industrial processes, and to do that we really need to be able to understand what shapes the composition and function of microbial communities,” Harcombe says. “In this study we were able to show that even in a spatially structured microbial community we can get highly repeatable evolutionary outcomes. It’s exciting because it suggests that in some cases we’ll be able to predict how microbial communities will change through time.”

Harcombe’s lab is now focused on further understanding the dynamics of microbial networks, including looking at what happens when communities are disrupted by things like the introduction of antibiotics or viruses.

“Minnesota’s an amazing place to be doing research like this,” he says. “We have incredible colleagues in ecology, evolution and behavior, as well as microbiology and biotechnology. The integrative approaches that are possible here will be critical for understanding the fundamental processes that shape the biological world, and applying those understandings to help society.”

–Mary Hoff

Posted 
November, 2018