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Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [8]

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nitrogen contains fourteen protons and fourteen neutrons, but lighter and heavier forms of nitrogen also exist, with fewer or more neutrons. Meselson and Stahl fed E. coli ammonia laced with heavy nitrogen in which each atom carried a fifteenth neutron. After the bacteria had reproduced for many generations, they extracted some DNA and spun it in a centrifuge. By measuring how far the DNA moved as it was spun, they could calculate its weight. They could see that the DNA from E. coli raised on heavy nitrogen was, as they had expected, heavier than DNA from normal E. coli.

Meselson and Stahl then ran a second version of the experiment. They moved some of the heavy-nitrogen E. coli into a flask where they could feed on normal nitrogen, with only fourteen neutrons apiece. The bacteria had just enough time to divide once before Meselson and Stahl tossed their DNA in the centrifuge. If Watson and Crick were right about how DNA reproduced, Meselson and Stahl knew what to expect. Inside each microbe, the heavy strands would have been pulled apart, and new strands made from light nitrogen would have been added to them. The DNA in the new generation of E. coli would be half heavy, half light. It should form a band halfway between where the light and heavy forms did. And that was precisely what Meselson and Stahl saw.

Watson and Crick might have built a beautiful model. But it took a beautiful experiment on E. coli for other scientists to believe it was also true.

A UNIVERSAL CODE

The discovery of E. coli’s sex life gave scientists a way to dissect a chromosome. It turned out that E. coli has a peculiar sort of sex, with one microbe casting out a kind of molecular grappling hook to reel in a partner. Its DNA moves into the other microbe over the course of an hour and a half. Élie Wollman and François Jacob, both at the Pasteur Institute in Paris, realized that they could break off this liaison. They mixed mutants together and let them mate for a short time before throwing them into a blender. Depending on how long the bacteria were allowed to mate, the recipient might or might not get a gene it needed to survive. By timing how long it took various genes to enter E. coli, Wollman and Jacob could create a genetic map. It turned out that E. coli’s genes are arrayed on a chromosome shaped in a circle.

Scientists also discovered that along with its main chromosome E. coli carries extra ringlets of DNA, called plasmids. Plasmids carry genes of their own, some of which they use to replicate themselves. Some plasmids also carry genes that allow them to move from one microbe to another. E. coli K-12’s grappling hooks, for example, are encoded by genes on plasmids. Once the microbes are joined, a copy of the plasmid’s DNA is exchanged, along with some of the chromosome itself.

As some scientists mapped E. coli’s genes, others tried to figure out how their codes are turned into proteins. At the Carnegie Institution in Washington, D.C., researchers fed E. coli radioactive amino acids, the building blocks of proteins. The amino acids ended up clustered around pellet-shaped structures scattered around the microbe, known as ribosomes. Loose amino acids went into the ribosomes, and full-fledged proteins came out. Somehow the instructions from E. coli’s DNA had to get to the ribosomes to tell them what proteins to make.

It turned out that E. coli makes special messenger molecules for the job. The first step in making a protein requires an enzyme to clamp on to a gene and crawl along its length. It builds a single-stranded version of the gene from RNA. This RNA can then move to a ribosome, delivering its genetic message.

How a ribosome reads that message was far from clear, though. RNA, like DNA, is made of four different bases. Proteins are combinations of twenty amino acids. E. coli needs some kind of dictionary to translate instructions written in the language of genes into the language of proteins.

In 1957, Francis Crick drafted what he imagined the dictionary might look like. Each amino acid was encoded by a string of three bases,

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