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2 14.2 The Genetic Code

Elizabeth Dahlhoff and OpenStaxCollege

Learning Objectives

By the end of this chapter, you will be able to do the following:

  • Explain more specific details of the “central dogma” of information flow
  • Describe the genetic code and how the nucleotide sequence prescribes the amino acid and the protein sequence

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), which substitutes for thymine (T) in RNA molecules. 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. 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.

Structures of the 20 amino acids found in proteins are shown below. Each amino acid is composed of an amino group (\(\text{N}{\text{H}}_{3}^{+}\)), a carboxyl group (COO–), and a side chain (blue). The side chain may be nonpolar, polar, or charged, as well as large or small. It is the variety of amino acid side chains that gives rise to the incredible variation of protein structure and function.

Structures of the twenty amino acids are given. Six amino acids—glycine, alanine, valine, leucine, methionine, and isoleucine—are non-polar and aliphatic, meaning they do not have a ring. Six amino acids—serine, threonine, cysteine, proline, asparagine, and glutamate—are polar but uncharged. Three amino acids—lysine, arginine, and histidine—are positively charged. Two amino acids, glutamate and aspartate, are negatively charged. Three amino acids—phenylalanine, tyrosine, and tryptophan—are nonpolar and aromatic.

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 Central Dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Instructions on DNA are transcribed onto messenger RNA. Ribosomes are able to read the genetic information inscribed on a strand of messenger RNA and use this information to string amino acids together into a protein. In prokaryotic organisms, mRNAs are translated directly into protein; in eukaryotes, mRNAs need to be translocated from the nucleus (where transcription occurs) into the cytosol, where protein synthesis occurs. Eukaryotic mRNA also needs to be processed and edited. This process is discussed in a later chapter. 

To make a protein, genetic information encoded by the DNA must be transcribed onto an mRNA molecule. The RNA is then processed by splicing to remove exons and by the addition of a 5' cap and a poly-A tail. A ribosome then reads the sequence on the mRNA, and uses this information to string amino acids into a protein.

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 degenerate. In other words, a given amino acid could be encoded by more than one nucleotide triplet. This was later confirmed experimentally. This demonstrated that three nucleotides specify each amino acid. These nucleotide triplets are called codons. The insertion of one or two nucleotides completely changed the triplet reading frame, thereby altering the message for every subsequent amino acid. Though insertion of three nucleotides caused an extra amino acid to be inserted during translation, the integrity of the rest of the protein was maintained.

Scientists painstakingly solved the genetic code by translating synthetic mRNAs in vitro and sequencing the proteins they specified.

The figure below shows the genetic code for translating each nucleotide triplet in mRNA into an amino acid or a termination signal in a nascent protein. (credit: modification of work by National Institutes of Health).

Figure shows all 64 codons. Sixty-two of these code for amino acids, and three are stop codons.

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 nonsense codons, or stop codons. Another codon, AUG, also has a special function. In addition to specifying the amino acid methionine, it also serves as the start codon to initiate translation. The reading frame for translation is set by the AUG start codon near the 5′ end of the mRNA.

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 something like a 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.

PRACTICE TRANSLATING A GENE

To get a feel for how this works, here is an exercise where you can transcribe a gene and translate it to protein using complementary pairing and the genetic code.

 

The deletion of two nucleotides shifts the reading frame of an mRNA and changes the entire protein message, creating a nonfunctional protein or terminating protein synthesis altogether.

Illustration shows a frameshift mutation in which the reading frame is altered by the deletion of two amino acids.

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.

Section Summary

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.

Review Questions

The AUC and AUA codons in mRNA both specify isoleucine. What feature of the genetic code explains this?

  1. complementarity
  2. nonsense codons
  3. universality
  4. degeneracy

4. degeneracy

How many nucleotides are in 12 mRNA codons?

  1. 12
  2. 24
  3. 36
  4. 48

3. 36 nucleic acids

Free Response

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.

Glossary

codon
three consecutive nucleotides in mRNA that specify the insertion of an amino acid or the release of a polypeptide chain during translation
degeneracy
(of the genetic code) describes that a given amino acid can be encoded by more than one nucleotide triplet; the code is degenerate, but not ambiguous
nonsense (stop) codon
one of the three mRNA codons that specifies termination of translation
reading frame
sequence of triplet codons in mRNA that specify a particular protein; a ribosome shift of one or two nucleotides in either direction completely abolishes synthesis of that protein

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14.2 The Genetic Code Copyright © by Elizabeth Dahlhoff and OpenStaxCollege is licensed under a Creative Commons Attribution 4.0 International License, except where otherwise noted.

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