It Pays to Plan Ahead


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 Prof. Yitzhak Pilpel, Dr. Orna Dahan and Amir Mitchell. Bacteria anticipate the future
We humans learn anticipation from a young age. For example, a baby may begin to calm down at the mere sight of its bottle; or a driver’s foot might twitch on the brake at a stoplight, ready to switch pedals as soon as the light turns green. It turns out that bacteria can also anticipate the future and even get ready to meet it. That’s the conclusion of research at the Weizmann Institute showing that, just as we’ve learned to expect that a red light will be followed by a green one, bacteria can “learn” to foresee certain regular changes in their environments and begin preparing for the next stage. This research recently appeared in Nature.
Prof. Yitzhak Pilpel, research student Amir Mitchell and Dr. Orna Dahan of the Weizmann Institute’s Molecular Genetics Department, and their research team asked whether natural selection can act as a “teacher,” conditioning single-celled organisms to respond to a “predictable” sequence of events. For instance, E. coli, a type of normally harmless bacteria found in the digestive tract, experience such regular changes as they cruise harmlessly from one end to the other. In particular, they find that one type of sugar – lactose – is invariably followed by a second sugar – maltose – soon afterward. Pilpel, Mitchell and Dahan checked the bacterium’s genetic response to lactose and discovered that in addition to the genes that enable it to digest lactose, the gene network for utilizing maltose was simultaneously partially activated. When they switched the order of the sugars, giving the bacteria maltose first, there was no corresponding activation of lactose genes, implying that bacteria have naturally learned to get ready for a serving of maltose after a lactose appetizer.
Another microorganism that experiences consistent change is wine yeast. As fermentation progresses, sugar and acidity levels change, alcohol levels rise, and the yeast’s environment heats up. The scientists found that when the wine yeast feels the heat, it begins activating genes for dealing with the stresses of the next stage. Further analysis showed that this anticipation and early response is an evolutionary adaptation that increases the organism’s chances of survival.
So far, bacteria and yeast were demonstrating the classical “conditioned response” famously demonstrated by the Russian scientist Ivan Pavlov in dogs. Pavlov trained his dogs to salivate in response to a stimulus by repeatedly ringing a bell before giving them food. In microorganisms, says Pilpel, “evolution over many generations replaces conditioned learning, but the end result is similar.” “In both evolution and learning,” says Mitchell, “the organism adapts its responses to environmental cues, improving its ability to survive.”
But Pavlov, in further experiments, demonstrated the learned nature of the dogs’ response: It could be unlearned, as well. When he stopped giving the dogs food after ringing the bell, the conditioned response faded until they eventually ceased salivating at its sound. Could bacteria “unlearn” the conditioning developed over many generations of evolution? To answer this question, the scientists conducted another Pavlovian experiment: They tested E. coli grown by Dr. Erez Dekel in the lab of Prof. Uri Alon of the Molecular Cell Biology Department, in an environment containing the first sugar, lactose, but lacking the maltose chaser. After several months, the bacteria evolved to stop activating their maltose genes at the taste of lactose, only turning them on when maltose was actually available.
Just as Pavlov’s dogs eventually stopped wasting their saliva in the absence of a reward, the bacteria appeared to learn that activating genes for no reason was counterproductive. “These findings showed us that there is a cost to advanced preparation, but that the benefits to the organism outweigh the costs in the right circumstances,” says Pilpel. What are those circum-stances? Based on the experimental evidence, the research team created a sort of cost/benefit model to predict the types of situations in which an organism could increase its chances of survival by evolving to anticipate future events. They are already planning a number of new tests for their model, as well as different avenues of experimentation based on the insights they have gained.
Pilpel and his team believe that the genetic conditioned response may be a widespread means of evolutionary adaptation that enhances survival in many organisms – one that may also take place in the cells of higher organisms, including humans. These findings could have practical implications, as well. Genetically engineered microorganisms for fermenting plant materials to produce biofuels, for example, might work more efficiently if they gained the genetic ability to prepare themselves for the next step in the process.
Prof. Yitzhak Pilpel’s research is supported by the Ben May Charitable Trust; the Minna James Heineman Stiftung; and Huguette Nazez, France.