Trade-offs are ubiquitous. They are the most powerful underlying forces driving all the constraints in life, in nature. The most severe one, perhaps, it the trade-off between change and stability. You’ve probably felt the tension of choice such a trade off imposes upon you multiple times. Should you apply for a PhD abroad, change your life upside down, or should you go on studying at your own collage, at the safe and warm place you got used to. Furthermore, perhaps unconsciously, most of the time you associate change with risk, and stability with safety. Going abroad is risky, but staying still feels safe. Anyway, this is not literally a matter of life and death, right?
Fourth chapter, named Risky Refuges, of the book Paradoxical Life (you definitely have to read the whole book, though) mentions such a trade off between change and stability, when the life of a bacteria is on the table. I would like to quote from A. Wagner, the author of the book, for a brief introduction,
"The bacteria in each colony have voracious appetites and divide so rapidly that a colony takes a mere two days to form. Its millions of inhabitants swiftly consume the food around them. Days after having formed, the colony begins to starve. Fortunately, bacteria have developed sophisticated strategies to evade starvation. One is a peculiar form of Russian roulette: some starving bacteria gamble with the ultimate risk, death.” [1]
The sophisticated strategies Wagner mentions has to do a lot with the transcription and repair mechanisms of the bacteria’s DNA, so let me come back what this paragraph means later, and talk about the DNA a little bit first.
Although DNA seems so magical and fascinating, after all, it’s a molecule. It’s constantly exposed to many intrinsic and extrinsic attacks, such as the metabolic waste (free radicals) the the bacteria itself produces, particles with high energy radiation from outside, or UV-light from the sun. All these influences hurts the DNA, and corrupts the information it contains, i.e., inducing DNA lesions. A corrupted DNA means corrupted proteins, that folds into corrupted enzymes, which are essential for the life of a cell. Eventually, a DNA that is not fixed regularly, will kill the cell.
As you may guess, evolution took care of this maintenance process. It is called the SOS response. DNA lesions that block replicative DNA polymerases - which are enzymes that are essential to DNA replication - induce the SOS system. For instance, DNA polymerase III (Pol III) is the primary enzyme involved in DNA replication in E. coli. During SOS induction, production of another DNA polymerase, called Pol IV, is increased. What Pol IV does is to interfere with Pol III, stopping replication and allowing time to repair DNA lesions. But DNA repair system is not error free. Another function of Pol IV is to perform translesion synthesis, which means allowing the replication of past DNA lesions. Translesion synthesis allows survival, however, as it is performed with low fidelity1, it introduces mutations [2].
So what does it all have to do with the starving bacteria? Keep in mind that DNA repair, like any other maintenance task going on in the bacteria, requires energy. When bacteria colony beings to starve, it has to decide on its priorities. It has to choose the tasks it will invest its limited energy on. Starvation induces the RpoS2 regulon3, i.e., genes which are under RpoS regulation. RpoS regulon induces the dinB gene [3], which is responsible of the production of Pol IV, the error-prone translesion synthesis polymerase in the SOS response mechanism mentioned above. Pol IV downregulates the DNA replication by blocking Pol III, which, in return, reduces the energy spent for DNA replication, but as a trade-off, introduces mutations due to translesion synthesis. This phenomena is called stress-induced mutagenesis (SIM).
Mechanism described above explains how DNA change accelerates in starving cells. Although the main reason seems to be energy conversation, many biologist think that this mechanism may be more than that. In fact, it may be a strategy for survival, the sophisticated strategies Wagner talks about.
“As unlikely as it seems, there may be method behind such sloppy DNA repair. It may be a gamble with enormous stakes.” [1]
Just for a second, think of what food means for an organism. Food is what you can digest to extract energy by using your enzymes. Enzymes are nothing but proteins produced by your DNA. When a bacteria starves, it means that what it considers as food is scarce. But there are other kinds of stuff out there that can be digested, only if you had the right enzyme to do so. By downregulating DNA repair, changing their DNA at random, bacteria gambles with its proteins. Most of the changes will probably kill it, but with a small probability, it has a chance to find the right gene that will produce the right enzyme to digest the novel food. What bacteria really does is to search for new genotypes that will change its phenotype for survival, in exchange for the risk of death.
This may be the most natural trade-off you can observe between change and stability. It makes you re-think the association between safety and stability, and similarly, the association between change and risk. I guess there is a lot to learn from the strategies driven by stressed organisms. At the end of the day, they are the ones who survived the natural selection.
"For now, just consider this question: What is risky and what is safe—from a cell’s perspective? To maintain DNA repair is certainly safe. Cells that keep up repair certainly will not die from corroding cell parts. To maintain DNA repair, however, may also be very risky: the cell’s inaction tacitly assumes that food will again become available. The chances of that happening may be nil. Conversely, shutting down DNA repair is obviously risky. It will eventually destroy the cell. But is it perhaps the only safe course of action? It might create the one and only survival strategy, the end of starvation and the formation of new life.” [1]
Footnotes
1. The fidelity of a DNA polymerase depends not the accurate replication of a desired template.
2. RpoS is an alternative sigma factor (a protein needed only for initiation of RNA synthesis) which controls genes that are expressed in response to nutrient deprivation (starvation).
3. Regulon is a collection of genes or operons under regulation by the same regulatory protein.
References
[1] Andreas Wagner, "Paradoxical Life: Meaning, Matter, and the Power of Human Choice”, Yale University Press, September 2009.
[2] O. Tenaillon, E. Denamur, I. Matic, “Evolutionary significance of stress-induced mutagenesis in bacteria”, Elsevier Trends in Microbiology, Vol.12 No.6, June 2004.
