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Genetics I 4
Introduction
Chimpanzees are set apart from all other organisms because their parents were chimpanzees and their off spring will also be chimpanzees. The study of genetics attempts to explain this process of heredity and it also plays a very signifi cant role in the modern world, from plant and animal breeding to human health and disease.
4.1 Chromosomes, genes, alleles and
mutation
A triplet of bases in the DNA molecule is transcribed into a triplet of bases in the mRNA molecule, which is then translated into a specifi c amino acid, as shown in Figure 4.2.
The process of DNA replication is complex and mistakes sometimes occur – a nucleotide may be left out, an extra one may be added, or the wrong one inserted. These mistakes are known as gene mutations.
The insertion of an incorrect nucleotide is called a base substitution mutation. When the DNA containing an incorrect nucleotide is transcribed and translated, errors may occur in the polypeptide produced.
Table 4.1 shows the amino acids that are specifi ed by diff erent mRNA codons. Most amino acids are coded for by more than one codon and so many substitution mutations have no eff ect on the fi nal polypeptide that is produced. For example, a mutation in the DNA triplet CCA into CCG would change the codon in the mRNA from GGU to GGC but it would still result in the amino acid glycine being placed in a polypeptide. Some substitution mutations, however, do have serious eff ects and an important human condition that results from a single base substitution is sickle-cell anemia.
C A G
transcription
DNA triplet
RNA triplet
amino acid translation
glutamine
G T C
C A G
Figure 4.2 The base sequence in DNA is decoded via transcription and translation.
Second base
U C A G
First base
U UUU
phenylalanine UCU
serine
UAU
tyrosine
UGU
cysteine U
Third base
UUC UCC UAC UGC C
UUA
leucine
UCA UAA
‘stop’
UGA ‘stop’ A
UUG UCG UAG UGG tryptophan G
C CUU
leucine
CCU
proline CAU
histidine CGU
arginine U
CUC CCC CAC CGC C
CUA CCA CAA
glutamine
CGA A
CUG CCG CAG CGG G
A AUU
isoleucine
ACU
threonine AAU
asparagine AGU
serine U
AUC ACC AAC AGC C
AUA ACA AAA
lysine
AGA
arginine A AUG methionine
or ‘start’ ACG AAG AGG G
G GUU
valine
GCU
alanine
GAU aspartic acid
GGU
glycine U
GUC GCC GAC GGC C
GUA GCA GAA glutamic
acid
GGA A
GUG GCG GAG GGG G
Table 4.1 To show the amino acids and their associated mRNA codons.
Gene a heritable factor that controls a specifi c characteristic, or a section of DNA that codes for the formation of a polypeptide Allele a specifi c form of a gene occupying the same gene locus or position (page 77) as other alleles of that gene, but diff ering from other alleles by small diff erences in its base sequence
Genome the whole of the genetic information of an organism
Gene mutation a change in the sequence of bases in a gene
There are several thousand human disorders that are caused by mutations in single genes and about 100
‘syndromes’ associated with chromosome abnormalities.
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Sickle-cell anemia – the result of a base substitution mutation Sickle-cell anemia is a blood disorder in which red blood cells become sickle shaped and cannot carry oxygen properly (Figure 4.3). It occurs most frequently in people with African ancestry – about 1% suff er from the condition and between 10% and 40% are carriers of it. Sickle-cell anemia is due to a single base substitution mutation in one of the genes that make hemoglobin, the oxygen-carrying pigment in red blood cells.
Hemoglobin is made up of four subunits, as shown in Figure 4.4 – two
α-chains and two β-chains. The 9 β-chains are aff ected by the sickle-cell mutation. To form a normal β-chain, the particular triplet base pairing in the DNA is:
Figure 4.4 The structure of a hemoglobin molecule showing the three-dimensional arrangement of the subunits that make it up.
G A G
C T C
G T G
C A C
The C–T–C on the coding strand of the DNA is transcribed into the mRNA triplet G–A–G, which in turn is translated to give glutamic acid in the polypeptide chain of the β-subunit.
If the sickle-cell mutation occurs, the adenine base A is substituted for thymine T on the coding strand, so the triplet base pairing becomes:
C–A–C on the coding strand of the DNA is now transcribed into the mRNA triplet G–U–G, which in turn is translated to give the amino acid valine. Valine replaces glutamic acid in the β-chain.
Figure 4.3 Scanning electron micrograph showing a sickle cell and normal red blood cells.
the two α-units
are shown in blue the two β-units
are shown in red
Only one strand of DNA is transcribed into mRNA for any gene. The transcribed strand is called the coding strand.
Valine has diff erent properties from glutamic acid and so this single change in the amino acid sequence has very serious eff ects. The resulting hemoglobin molecule is a diff erent shape, it is less soluble and when in low oxygen concentrations, it deforms the red blood cells to give them a sickle shape. Sickle cells carry less oxygen, which results in anemia. They are also rapidly removed from the circulation, leading to a lack of red blood cells and other symptoms such as jaundice, kidney problems and enlargement of the spleen.
1 The β-chain of the hemoglobin molecule contains 146 amino acids. How many nucleotides are needed to code for this protein?
2 a List the two structural components of a eukaryotic chromosome.
b How does this structure differ from that of a prokaryotic chromosome?
3 Defi ne the following terms.
a ‘gene’
b ‘allele’
c ‘genome’
d ‘gene mutation’
4 What is meant by the term ‘base substitution mutation’?
5 a In the normal allele for the β-chain of hemoglobin, there is a triplet on the coding strand of the DNA that is C–T–C. In people suffering from sickle-cell anemia, what has this triplet mutated to?
b Because of this mutation, one amino acid in the polypeptide chain of the β-subunits in hemoglobin is abnormal. Name the normal amino acid and also the amino acid resulting from the sickle-cell mutation.
c Explain why this mutation leads to sickle-cell anemia.
6 The following is a sequence of bases in a DNA molecule that has been transcribed into an RNA molecule.
CGGTAAGCCTA
Which is the correct sequence of bases in the RNA molecule?
A CGGTAAGCCTA B GCCATTGGAT C CGGUAAGCCUA D GCCUTTCGGAU
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