Nucleic Acids and DNA Replication

Lessons

Senior 5 · Biology

Nucleic Acids and DNA Replication

5 lessons

Lesson 3 of 5

Genes and the genetic code

25 min

Twenty thousand genes in three billion letters

The human genome, one full set of chromosomes, is about 3.2 billion base pairs long. When it was sequenced, biologists expected to find perhaps 100 000 genes. The count came out at only about 20 000 protein-coding genes, and their coding sequences make up less than 2 % of the DNA. So what is a gene, and how does a string of four bases spell out a protein made of twenty different amino acids? This lesson answers both questions; Unit 5 then follows the code as a protein is built.

Definition

Gene: a sequence of nucleotides in DNA, at a particular position on a chromosome, that codes for a polypeptide or for a functional RNA such as tRNA or rRNA.

Locus (plural loci): the position of a gene on a chromosome. Allele: one of the different forms of a gene at the same locus.

Exon: a section of a gene that codes for part of the polypeptide. Intron: a non-coding section within a gene, copied into RNA but removed before the RNA is used.

Genome: all the genetic material of an organism.

The nature of genes

In 1941 George Beadle and Edward Tatum found that each mutant of the bread mould Neurospora lacked a single enzyme, and proposed "one gene, one enzyme". The idea was later refined to one gene, one polypeptide, because many proteins, such as haemoglobin, are built from several different polypeptides, each coded by its own gene. Some genes code not for a polypeptide but for an RNA that does a job itself, such as tRNA or rRNA.

Most eukaryotic genes are split: coding exons alternate with non-coding introns. Introns are often much longer than the exons.
A promoter next to the gene is where the enzyme RNA polymerase binds to start reading it.
Prokaryotic genes usually have no introns, and bacteria pack their genes closely with little DNA between them.
Much of the rest of the genome is non-coding: regulatory sequences that switch genes on and off, repeated sequences, and the DNA of centromeres and telomeres.

Worked example 1: exons and amino acids

A human gene is 12 000 base pairs long from its first exon to its last. Its three exons together contain 1 500 coding nucleotides, ending in a stop codon. Calculate (a) the percentage of the gene that is intron, and (b) the number of amino acids in the polypeptide.

(a) Introns $= 12\,000 - 1\,500 = 10\,500$ base pairs; $\frac{10\,500}{12\,000} \times 100 = 87.5\,\%$ .
(b) Codons $= \frac{1\,500}{3} = 500$ . The last is a stop codon, which codes for no amino acid, so the polypeptide has $500 - 1 = 499$ amino acids.

Definition

Genetic code: the set of rules by which a sequence of bases in DNA (and its mRNA copy) specifies the sequence of amino acids in a polypeptide.

Codon: a sequence of three bases in mRNA (or DNA) that codes for one amino acid or for "stop".

Reading frame: the way a base sequence is divided into consecutive triplets, fixed by the start codon.

The structure of the genetic code

Why three bases? There are 20 amino acids but only 4 bases. One base per amino acid gives $4^{1} = 4$ words; two bases give $4^{2} = 16$ , still too few; three bases give $4^{3} = 64$ , more than enough. So the code is a triplet code. Its properties are:

Property	Meaning	Example
Triplet	Three bases (a codon) code for one amino acid	UUU codes for phenylalanine
Degenerate	Most amino acids have more than one codon: 61 codons code for 20 amino acids	Glycine: GGU, GGC, GGA and GGG
Non-overlapping	Each base is part of only one codon	AUGUUU is read AUG UUU, never also UGU
No punctuation	Codons are read one after another, without gaps, from a fixed start	Deleting one base shifts every later codon (Figure 2)
Start and stop signals	AUG (methionine) starts every polypeptide; UAA, UAG and UGA mean "stop"	AUG … UAA
Universal	The same codons code for the same amino acids in almost all organisms	A human insulin gene works in bacteria

How the code was cracked

In 1961 Francis Crick, Sydney Brenner and colleagues studied a virus gene. Adding or deleting one base destroyed the gene's function, and so did two; but adding three bases close together often restored it, because the reading frame was put right again. This showed the code is read in threes from a fixed start. In the same year Marshall Nirenberg and Heinrich Matthaei added an artificial mRNA made only of uracil (poly-U) to a cell-free extract of bacteria and obtained a polypeptide made only of phenylalanine: UUU was the first codon to be read. By 1966 all 64 codons had been assigned.

Worked example 2: the logic of the frameshift experiment

Use the sentence THE CAT ATE THE RAT as a model gene read in three-letter words.

Delete the first E: THC ATA TET HER AT… Every word after the deletion is nonsense.
Delete one letter from each of the first three words (E from THE, A from CAT, E from ATE). The letters left, THCTATTHERAT, read in threes give THC TAT THE RAT. Only the region between the first and last deletion is wrong; the reading frame is restored after the third deletion.
Conclusion: if the code were read in pairs, deleting two letters would restore the frame; if in fours, four would. Restoration after three shows a triplet code.

Cognito: "A-Level Biology - Genetic Code". Watch for the meaning of degenerate, non-overlapping and universal, and for how to use a codon table, which you will need in Unit 5.

Warning

Common mistakes

"Degenerate means the code has mistakes." It means that several codons can code for the same amino acid. It is not ambiguous: each codon codes for only one amino acid.
Counting the stop codon as an amino acid when working out the length of a polypeptide.
"All DNA is made of genes." In humans, less than 2 % of the DNA codes for proteins.

Tip

Length calculations: number of amino acids = (number of coding nucleotides ÷ 3) − 1 if the stop codon is included. Use the exons only; introns are removed before translation.

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Practice: genes and the genetic code

Define gene, locus and allele.
Explain why the genetic code must be at least a triplet code.
Explain what is meant by saying the code is (a) degenerate, (b) non-overlapping, (c) universal.
How many codons code for amino acids, and how many are stop codons?
A polypeptide has 320 amino acids. What is the minimum number of nucleotides in the mRNA that codes for it, including the stop codon?
Explain why "one gene, one enzyme" was changed to "one gene, one polypeptide".
Why does a deletion of one base near the start of a gene usually have a bigger effect than a deletion near the end?
Suggest why the universality of the code is evidence that all life shares a common ancestor.

Show answersHide answers

Gene: a sequence of DNA nucleotides at a particular locus that codes for a polypeptide or functional RNA. Locus: the position of a gene on a chromosome. Allele: a different form of the same gene.
Four bases taken one or two at a time give only 4 or 16 combinations, fewer than 20 amino acids; three at a time give 64, which is enough.
(a) Most amino acids are coded by more than one codon. (b) Each base belongs to only one codon. (c) The same codons code for the same amino acids in almost all organisms.
61 code for amino acids; 3 are stop codons.
$(320 + 1) \times 3 = 963$ nucleotides.
Some proteins are made of several different polypeptides, each coded by a separate gene, and many proteins are not enzymes (e.g. haemoglobin, keratin).
It causes a frameshift: every codon after the deletion is changed, so a deletion near the start changes almost all the amino acids, while one near the end changes only a few.
An arbitrary code shared by bacteria, plants and animals is most simply explained by inheritance from one ancestor in which the code was fixed, not by independent invention many times.

Key points

A gene codes for a polypeptide or a functional RNA; eukaryotic genes have exons and introns.
The code is triplet, degenerate, non-overlapping, read without gaps from a start codon, and universal.
64 codons: 61 for amino acids, 3 stop codons; AUG = start (methionine).
Frameshift experiments (Crick, Brenner) and poly-U (Nirenberg, Matthaei) cracked the code.

Sources and credits

Written by Ganzaa. The genome figures follow the National Human Genome Research Institute, genome.gov. The experiments described are F. H. C. Crick and colleagues, Nature 192 (1961), and M. W. Nirenberg and J. H. Matthaei, PNAS 47 (1961). No text was copied.
Video: A-Level Biology - Genetic Code, Cognito, embedded from YouTube.

Figures 1 and 2, the tables, the worked examples and the practice questions are written by Ganzaa.

1Twenty thousand genes in three billion letters

2The nature of genes

3The structure of the genetic code

How the code was cracked

Twenty thousand genes in three billion letters

The nature of genes

The structure of the genetic code