By Robert Hazen, George Mason University
As we all know, proteins are the workhorses of life. Of equal importance is the DNA, which dictates its function. Thus, we have a code on the one hand, which is carried in DNA, and proteins on the other hand, and we had to get from one to the other. It sought to answer the question: How do we make proteins? How do genetics work? Of what significance is the genetic code?
Gene Mutations
The DNA breakthrough, all of a sudden, unified genetics by providing a common conceptual basis, a simple chemical basis for understanding out genetics works. And yet, a big challenge that confronted scientists was that, whatever the nature of the genetic code, it had to somehow convert that four-letter alphabet, the A, C, T, and G of DNA, into a correct sequence of amino acids—and there are 20 amino acids—to make a protein.
Since geneticists were well aware that one gene equals one protein, progress, with respect to understanding genetic code, was made by studying gene mutations. It involved, basically, studying how things work when something goes wrong. Some mutations were known to result in the replacement of one amino acid, for example, with another one, such as in the case of the sickle-cell disease.
The Genetic Code
More clues were revealed in the late 1950s by pioneering genetic research on mutant forms of the simple bacterium E. coli. Scientists would document different mutants, different examples of E. coli where things went wrong, and then they looked at where the genetic words varied before and after, and found out what misspellings in the proteins led to those mutations.
It turned out from these experiments, that it was very likely that three letters in each DNA corresponded to one amino acid in each protein, and so an additional clue was found. Thus, the way in which we take those three-letter groupings, or codons, in DNA and link them up to amino acid was called the genetic code.
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Genetic Process and the RNA
It was during a decade of intense and often highly competitive research that biologists discovered these details: the process by which DNA leads to the synthesis of a protein. Ultimately, the key to understanding the genetic process was this: one has to take molecular information and convert it into an actual protein. Scientists discovered that the synthesis depends on a third type of molecule: ribonucleic acid, or RNA.
RNA is very closely related to DNA, and there are only a few differences. Here’s what they are: each RNA is a single-stranded molecule of nucleotides—not a double helix, like DNA, but a single-stranded polymer.
Another difference is that the sugar ribose substitutes for deoxyribose in the long backbone of that polymer. Finally, there is a slightly different base: uracil, or U, substitutes for thymine, or T; another little wrinkle that one has to keep in mind. With the exception of those three little differences, RNA and DNA are very much alike.
The Messenger RNA
There are three different forms of RNA that participate in protein synthesis, and first is messenger RNA. Messenger RNA copies the base sequence from DNA, and this is how it works. One has to think of one of those zippers on an old sleeping bag, or an old jacket, which is broken, so that even though the jacket’s zipped up, or the zipper is zipped up, there’s an opening in the middle?
In this case, one can see the two sides of the zipper exposed where they’re not supposed to be. That’s exactly what a certain kind of enzyme does to DNA. It unzips a central portion of the DNA, and it exposes one portion, one gene, of the DNA.
RNA nucleotides then zip in, and they form a template, a copy of that one stretch of DNA. They form a messenger RNA, which is a single-stranded molecule which contains all the information one needs to make a single gene. The genetic code, then, relates to a specific group of nucleotides that correspond to specific amino acids in a protein.
The Combination on Messenger RNA
This was deciphered in the early 1960s by making synthetic messenger RNA chains. It was done by making a synthetic RNA and adding it to protein-synthesizing machinery in E. coli, noting what protein the E. coli makes when they sneak in this extra messenger RNA.
The first breakthrough came when workers at the National Institutes of Health used a synthetic RNA containing exclusively uracil basis. The unique protein produced was made entirely of the single amino acid, phenylalanine. That reveals that the combinations of three U, the UUU combination on messenger RNA, corresponded to the protein phenylalanine. If we have a long messenger RNA made only of U, we’d get a long protein made only of phenylalanine. That, clearly, was the first step in deciphering the genetic code.
Many additional experiments went on to reveal the spelling of all the three-letter words: the three-base words, or codons, of the genetic code.
Common Questions about Deciphering Genetic Code
Since geneticists were well aware that one gene equals one protein, progress, with respect to understanding genetic code, was made by studying gene mutations. It involved, basically, studying how things work when something goes wrong.
The key to understanding the genetic process was this: one has to take molecular information and convert it into an actual protein. Scientists discovered that the synthesis depends on a third type of molecule: ribonucleic acid, or RNA.
Each RNA is a single-stranded molecule of nucleotides—not a double helix, like DNA, but a single-stranded polymer. Another difference is that the sugar ribose substitutes for deoxyribose in the long backbone of that polymer. Finally, there is a slightly different base: uracil, or U, substitutes for thymine, or T; another little wrinkle that one has to keep in mind.
