3-5-2. The Genetic Code
The cellular process of transcription generates messenger RNA (mRNA), a mobile molecular copy of one or more genes with an alphabet of A, C, G, and uracil (U). Translation of the mRNA template converts nucleotide-based genetic information into a protein product. Protein sequences consist of 20 commonly occurring amino acids; therefore, it can be said that the protein alphabet consists of 20 letters (Figure 1). Each amino acid is defined by a three-nucleotide sequence called the triplet codon. Different amino acids have different chemistries (such as acidic versus basic, or polar and nonpolar) and different structural constraints. Variation in amino acid sequence gives rise to enormous variation in protein structure and function.
The Central Dogma: DNA Encodes RNA; RNA Encodes Protein
The flow of genetic information in cells from DNA to mRNA to protein is described by the
The Genetic Code Is Degenerate and Universal
Given the different numbers of “letters” in the mRNA and protein “alphabets,” scientists theorized that combinations of nucleotides corresponded to single amino acids. Nucleotide doublets would not be sufficient to specify every amino acid because there are only 16 possible two-nucleotide combinations (42). In contrast, there are 64 possible nucleotide triplets (43), which is far more than the number of amino acids. Scientists theorized that amino acids were encoded by nucleotide triplets and that the genetic code was
Scientists painstakingly solved the genetic code by translating synthetic mRNAs in vitro and sequencing the proteins they specified (Figure 3).
In addition to instructing the addition of a specific amino acid to a polypeptide chain, three of the 64 codons terminate protein synthesis and release the polypeptide from the translation machinery. These triplets are called
The genetic code is universal. With a few exceptions, virtually all species use the same genetic code for protein synthesis. Conservation of codons means that a purified mRNA encoding the globin protein in horses could be transferred to a tulip cell, and the tulip would synthesize horse globin. That there is only one genetic code is powerful evidence that all of life on Earth shares a common origin, especially considering that there are about 1084 possible combinations of 20 amino acids and 64 triplet codons.
Link to Learning
Transcribe a gene and translate it to protein using complementary pairing and the genetic code at this site.
Degeneracy is believed to be a cellular mechanism to reduce the negative impact of random mutations. Codons that specify the same amino acid typically only differ by one nucleotide. In addition, amino acids with chemically similar side chains are encoded by similar codons. This nuance of the genetic code ensures that a single-nucleotide substitution mutation might either specify the same amino acid but have no effect or specify a similar amino acid, preventing the protein from being rendered completely nonfunctional.
Scientific Method Connection
Which Has More DNA: A Kiwi or a Strawberry?
Question: Would a kiwifruit and strawberry that are approximately the same size (Figure 5) also have approximately the same amount of DNA?
Background: Genes are carried on chromosomes and are made of DNA. All mammals are diploid, meaning they have two copies of each chromosome. However, not all plants are diploid. The common strawberry is octoploid (8n) and the cultivated kiwi is hexaploid (6n). Research the total number of chromosomes in the cells of each of these fruits and think about how this might correspond to the amount of DNA in these fruits’ cell nuclei. Read about the technique of DNA isolation to understand how each step in the isolation protocol helps liberate and precipitate DNA.
Hypothesis: Hypothesize whether you would be able to detect a difference in DNA quantity from similarly sized strawberries and kiwis. Which fruit do you think would yield more DNA?
Test your hypothesis: Isolate the DNA from a strawberry and a kiwi that are similarly sized. Perform the experiment in at least triplicate for each fruit.
Record your observations: Because you are not quantitatively measuring DNA volume, you can record for each trial whether the two fruits produced the same or different amounts of DNA as observed by eye. If one or the other fruit produced noticeably more DNA, record this as well. Determine whether your observations are consistent with several pieces of each fruit.
Analyze your data: Did you notice an obvious difference in the amount of DNA produced by each fruit? Were your results reproducible?
Draw a conclusion: Given what you know about the number of chromosomes in each fruit, can you conclude that chromosome number necessarily correlates to DNA amount? Can you identify any drawbacks to this procedure? If you had access to a laboratory, how could you standardize your comparison and make it more quantitative?
The genetic code refers to the DNA alphabet (A, T, C, G), the RNA alphabet (A, U, C, G), and the polypeptide alphabet (20 amino acids). The Central Dogma describes the flow of genetic information in the cell from genes to mRNA to proteins. Genes are used to make mRNA by the process of transcription; mRNA is used to synthesize proteins by the process of translation. The genetic code is degenerate because 64 triplet codons in mRNA specify only 20 amino acids and three nonsense codons. Almost every species on the planet uses the same genetic code.
The AUC and AUA codons in mRNA both specify isoleucine. What feature of the genetic code explains this?
How many nucleotides are in 12 mRNA codons?
Imagine if there were 200 commonly occurring amino acids instead of 20. Given what you know about the genetic code, what would be the shortest possible codon length? Explain.
For 200 commonly occurring amino acids, codons consisting of four types of nucleotides would have to be at least four nucleotides long, because 44 = 256. There would be much less degeneracy in this case.
Discuss how degeneracy of the genetic code makes cells more robust to mutations.
Codons that specify the same amino acid typically only differ by one nucleotide. In addition, amino acids with chemically similar side chains are encoded by similar codons. This nuance of the genetic code ensures that a single-nucleotide substitution mutation might either specify the same amino acid and have no effect, or may specify a similar amino acid, preventing the protein from being rendered completely nonfunctional.