REHOVOT, ISRAEL—June 17, 2009—Bacteria can anticipate a future event and prepare for it, according to new research at the Weizmann Institute of Science. In a paper that appeared in the June 17, 2009 issue of Nature, Prof. Yitzhak Pilpel, doctoral student Amir Mitchell, and research associate Dr. Orna Dahan of the Institute’s Department of Molecular Genetics, together with Prof. Martin Kupiec and Gal Romano of Tel Aviv University, examined microorganisms living in environments that change in predictable ways. Their findings show that these microorganisms’ genetic networks are hard-wired to “foresee” what comes next in the sequence of events and begin responding to the new state of affairs before its onset.
E. coli bacteria, for instance, which normally cruise harmlessly down the digestive tract, encounter a number of different environments on their way. In particular, they find that one type of sugar — lactose — is invariably followed by a second sugar — maltose — soon afterward. Prof. Pilpel and his team checked the bacteria’s genetic response to lactose and found that, in addition to the genes that enable it to digest lactose, the gene network for utilizing maltose was 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 changes is wine yeast. As fermentation progresses, sugar and acidity levels change, alcohol levels rise, and the yeast’s environment heats up. Although the system was somewhat more complicated than that of E. coli, the scientists found that when the wine yeast feel the heat, they begin 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.
Ivan Pavlov first demonstrated this type of adaptive anticipation, known as a conditioned response, in dogs in the 1890s. He trained the dogs to salivate in response to a stimulus by repeatedly ringing a bell before giving them food. In the microorganisms, says Prof. 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.” Romano: “This is not a generalized stress response, but one that is precisely geared to an anticipated event.”
To see whether the microorganisms were truly exhibiting a conditioned response, Prof. Pilpel and Mitchell devised a further test for the E. coli based on another of Pavlov’s experiments. When Pavlov stopped giving the dogs food after ringing the bell, the conditioned response faded until they eventually ceased salivating at its sound. The scientists did something similar, using bacteria grown by Dr. Erez Dekel, in the lab of Prof. Uri Alon of the Weizmann Institute’s Department of Molecular Cell Biology, in an environment containing the first sugar, lactose, but not following it up with maltose. After several months, the bacteria had evolved to stop activating their maltose genes at the taste of lactose, only turning them on when maltose was actually available.
“This 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 Prof. Pilpel. What are those circumstances? 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. The researchers 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.
Prof. Pilpel and his team believe that 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 and Madame Huguette Nazez, Paris, France.The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.
