Introduction

Proteins are responsible for orchestrating nearly every cell function. Therefore, proteins also
influence most of the traits displayed by multicellular organisms. So, how do cells know how to
make the hundreds or thousands of different proteins that they need?
DNA contained in cells is a blueprint for making proteins (Figure 16.1). Each chromosome is a
single molecule of DNA wound tightly around proteins. Segments of the DNA molecule, called
genes, code for the order of amino acids in each protein. Both genes and the proteins they encode
are absolutely essential to life as we know it.

The Genetic Code

DNA contains the genes that serve as the blueprint for making proteins. Each protein has a
unique sequence of amino acids. Since different amino acids have different chemistries (such as
acidic vs. basic, or polar vs. nonpolar), the order of amino acids in a protein determines how the
protein folds, thereby determining the shape and function of the protein. The order of amino
acids in a protein is coded for by the gene for that protein.
The Central Dogma: DNA Encodes mRNA and mRNA Encodes Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by
the Central Dogma of molecular biology (Figure 16.2). When a cell needs a particular protein,
the gene that codes for that protein is activated and a single-stranded mRNA copy is made of the
gene, in a process called transcription. The code copied into the mRNA is then used to
determine the order of amino acids in the protein, in a process called translation. The copying of
DNA to RNA is relatively straightforward, with one nucleotide being added to the mRNA strand
for every nucleotide read in the DNA strand. The translation to protein is a bit more complex
because three mRNA nucleotides correspond to one amino acid in the polypeptide sequence
(Figure 16.2).
Figure 16.2 The central dogma of molecular biology. Segments of DNA, called genes, are
transcribed into mRNA copies. mRNA is then “read” in three-nucleotide codons to specify the
order of amino acids in a protein.

The Genetic Code Is Universal and Redundant

How does the order of nucleotides in an mRNA specify the order of amino acids in a protein?
mRNA is “read” in three nucleotide segments called codons. Since RNA has four nucleotides
(A, C, U, and G), there are 64 (43 ) possible combinations of three nucleotides (Figure 16.3). 61
of these codons code for one of the 20 common amino acids. The other three are called stop
codons or nonsense codons because they do not code for an amino acid.

Figure 16.3 The genetic code allows cells to translate each nucleotide triplet in mRNA into an
amino acid or a termination signal in a protein. (credit: modification of work by NIH)

Scientists painstakingly solved the genetic code by translating synthetic mRNAs in vitro and
sequencing the proteins they specified (Figure 16.4). Once all of the codons were known, they
discovered some important features of the code.
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
Since there are more nucleotide triplets than there are amino acids, the genetic code
is redundant. In other words, a given amino acid can be encoded by more than one nucleotide
triplet. Redundancy reduces the negative impact of random mutations. Codons that specify the
same amino acid typically only differ by one nucleotide, usually the third one. For example,
ACU, ACC, ACA and ACG all code for the amino acid threonine. In addition, amino acids with
chemically similar side chains are encoded by similar codons. For example, UGU and UGC code
for the amino acid cysteine, while AGU and AGC code for the amino acid serine. Cysteine and
serine both have polar side chains that are very similar in size and other properties. Thus, the
redundancy of the genetic code ensures that a single- nucleotide substitution mutation might
specify either the same amino acid or a similar amino acid, preventing the protein from being
rendered completely nonfunctional.

While 61 of the 64 codons specify the addition of a specific amino acid to a polypeptide chain,
the remaining three 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.

Elucidating the Genetic Code

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 (4 3 ). The
fact that amino acids were encoded by nucleotide triplets was confirmed experimentally by
Francis Crick and Sydney Brenner. They inserted one, two, or three nucleotides into the ge ne of
a virus. When one or two nucleotides were inserted, the protein was not made. When three
nucleotides were inserted, the protein was synthesized and functional. This demonstrated that
three nucleotides specify each amino acid.The nucleotide triplets that code for amino acids 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 (Figure 16.4). 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.

Figure 16.4 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.
Exceptions to the Central Dogma

Many genes code for RNA molecules that do not function as mRNAs and are therefore not
translated into proteins. Some RNAs, called rRNA, form parts of the ribosomes. Others form
transfer RNAs, or tRNA, which help with translation. Still others can regulate which genes are
expressed.

Another exception to the central dogma is in some cases, information flows backwards as is seen
in certain viruses called retroviruses. These viruses have genes made up of RNA and when
retroviruses infect a cell, the virus has to synthesize a DNA version of the RNA genes using a
specialized viral polymerase called reverse transcriptase. The human immunodeficiency virus
(HIV), which causes AIDS, is a retrovirus and many of the prescribed drugs used for AIDS
patients target the HIV reverse transcriptase.