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Articles: Science
The wise molecular biologist tells us the tale ....
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Once upon a time, a plasmid met a cell, and they struck up a conversation. Saith the plasmid, 'Kind cell, I bring thee a gene for antibiotic resistance, and if you let me in, I shall repay you by showing you how to make an enzyme that might save your life one day.' The cell replied with annoyance, 'What use hath I for the likes of thee? My food is all gone, I'm freezing my pili off, and you think my biggest problem is antibiotics? Maybe you're just a selfish gene, looking for a cell to make copies of you. Begone!' The plasmid smoothed out his supercoils, dodged a DNase, and tried to think of a suitable reply. Just then, a massive wave of thermal energy struck them both, and it was all he could do to not lose his footing, standing as he was on the cell membrane. The plasmid trembled, partly to distribute the energy uniformly to his vibrotational degrees of freedom, but mostly at the thought of how painful thermal denaturation might be. Fortunately, it was not coming to that. Not this time. The temperature was high enough to pop a few hydrogen bonds, and his strands were breathing a bit, but he was covalently closed after all. He could handle it! The cell was not so lucky, however. His membrane, which had been reasonably firm to this point, began to swirl and form vortices, and lost its smooth surface. The cell had gotten used to the cold temperatures by boosting the fraction of short chain and unsaturated fatty acids in his membrane. While it gave the membrane a good consistency in the icy cold, it was completely wrong for this new, higher temperature. The van der Waals interactions weren't strong enough to maintain cohesion, and errant lipids were now leaping through the bilayer like divers at a mosh pit. Huge patches of the membrane were involuting, bringing massive gulps of medium inside. The cell was just seconds away from a complete membrane breach! Then, as quickly as it had started, the problem was over. The buzz of thermal energy was drawn away by some unseen entropic sink, and dissipated. The membrane returned to its glassy-smooth state. The plasmid was now inside the cell, having been carried through the membrane in its moment of weakness, but the cell was too preoccupied to notice the uninvited guest. The cell was using his last remaining energy to bail out the excess liquid, and set his ion gradients to rights. When he thought he could do no more, that his determined course would be senescence and death, a warm flow of fresh medium restored his spirits. 'Ah! Tryptone, and yeast extract', he said as he gratefully derepressed half a dozen operons. His ribosomes got right to work, making the enzymes that would help to catabolize the new food source and restore the structure of the cell to full health. He almost exclaimed, 'I thought Darwin had me for sure that time!' but being a cell with little memory he had already forgotten the privations of a few minutes earlier. Thirty minutes passed, and he found himself cast onto a wide surface that was warm and rich in nutrients. 'Not bad', he said. I could live like this for generations!' But then, the horrible sounds of dying cells reached him. All around him, his brethren were being killed by an unseen attacker. An antibiotic was there, and was destroying the entire population. Oh the humanity! He braced himself for death, but then ... nothing happened. He was alive! 'Remember me?', said the plasmid? 'I told you that I might save your life one day, and now it has come to pass.' The plasmid, which had gone unnoticed since the thermal catastrophe, had been copied several times and transcribed by the cellular machinery. It had provided a gene that encoded an enzyme that destroyed the antibiotic before it even got into the cell. Although more antibiotic was diffusing into the neighborhood, the enzyme was on the job, and prevented it from doing any damage. 'Yes, you were right', said the cell. 'I am grateful that you transformed me, and now that I have a logical explanation for my good health, I don't have to develop survivor guilt either. Stick with me, plasmid, and I'll make sure you are provided with a high copy number.' The generations passed, and the cell divided many times. Each time there was fission, the two daughter cells received an inheritance of plasmid copies. There was widespread prosperity. I would say 'They lived happily ever after', but sadly that is not the end of the story. The daughter cells grew into a prodigious colony, and soon had destroyed so much of the antibiotic in the immediate vicinity that the real danger had passed. Some cells that had not perished in the original attack even managed to survive and grow nearby - little 'satellite colonies' seeking refuge from the high levels of antibiotic elsewhere. Then the cells in the big colony became lazy. The plasmid was not replicated to the same high copy number - it no longer served the interests of the cell to do so. Sometimes, daughter cells did not inherit even a single copy of the plasmid! As the colony aged and grew, the proportion of cells that carried the plasmid became less and less. The colony actually believed itself to be quite progressive on this point. Some of the more strident cells even argued: 'Why should young cells be forced to make enzymes that they don't need?' They said 'We want to evolve higher order characteristics, not merely regurgitate the knowledge that served our great-great-great grandcell!' Before long it was unfashionable to carry the plasmid, though a few still did, but the colony grew faster without the added responsibility of the added synthesis. One day, a toothpick scraped the colony from a plate and carried it high into the sky. 'At last,' the progressive cells thought, 'we are entering a bold new era in which we are going to be able to realize our true genetic potential!' The toothpick was dropped into a tube of fresh medium. The fresh medium had fresh antibiotic. What happened next is almost too horrible to tell. The cells that still carried the plasmid lived of course. They produced the enzyme that destroyed the antibiotic. The cells that had not inherited the plasmid were unworried at first, because they thought that a protective shield of enzyme could be built by the others, but being in liquid medium there was no hope for them. The antibiotic was not limited by diffusion, as it had been on the plate, and they were soon overcome. The few wise cells that had not lost their plasmid went on to eternal storage in glycerol stocks, and were written about in books and famous journals. They were grown in huge 10,000 liter fermentation tanks, and provided with the very richest medium that had ever been made! The end.

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