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Summary of 18.1
A point mutation is a change in a single base pair. These can be transitions or transversion.
Silent, missense, nonsense, and frameshift mutations may occur within the coding region of a gene
(see Table 18.1, Figure 18.1)
Mutation may also occur within noncoding regions of a gene and affect gene expression
Changes in chromosome structure can have a position effect that alters gene expression (see Figure
18.2, 18.2)
With regard of timing, mutation can occur in germ-line or in somatic cell (see Figure 18.4, 18.5)
Changes in chromosome structure and number are Gene Mutations Can Alter the Coding Sequence
mutations because the genetic material has been altered of a Gene
in a way that can be inherited. Changes in chromosome
structure and number affect the expression of many Silent Mutations: Those that do not alter
genes. In comparison, a gene mutation is relatively small amino acids sequence of the polypeptide even
change in DNA structure that affect a single gene. though the nucleotide sequence has changed.
o occur the third base, meaning that
amino acid is not changed.
Gene Mutations are Molecular Changes in the DNA
sequence of a Gene Missense Mutations: Base substitution in
A gene mutation occurs when the sequence of the DNA which an amino acid change does occur.
within a gene is altered in a permanent way. Sickle Cell Disease: Involves a mutation
A point mutation is a change in a single base pair in the β-goblin gene, which alters the
within the DNA. For example, the DNA sequence shown polypeptide sequence, so the sixth
here has been altered by a base substitution, in which one amino acid is changed from glutamic
base is substituted for another. acid (glu) to valine (val) which alters
the structure and function of the
5’-AACGCTAGATC-3’ 5’-AACGCGAGATC-3’ hemoglobin.
3’-TTGCGATCTAG-3’ 5’-TTGCGCTCTAG-3’ Under low oxygen conditions,
the red blood cell assumes
A change of pyrimidines to another, such as C to T sickle shape.
or purine to another, such as A to G is called transition.
This type of mutation is more common than a Nonsense Mutations: Involves a change from a
transversion, in which purines and pyrimidines are normal codon to a stop codon. Thus,
interchanged. terminating the translation of polypeptides
Besides base substitution, a short sequence of earlier than expected.
DNA may be deleted from or added to the chromosomal
DNA. Frameshift Mutations: Involves the addition or
deletion of several nucleotides that is not
5’-AACGCTAGATC-3’ 5’-AACGCTC-3’ divisible by three.
o This is a shift because codons are read
3’-TTGCGATCTAG-5’ 3’-TTGCGAG-5’
in multiple of three codons.
o The translation of the mRNA results in
5’-AACGCTAGATC-3’ 5’-AACAGTCGCTAGATC-3’
a different amino acid sequence
3’-TTGCGATCTAG-5’ 3’-TTGTCAGCGATCTAG-3’
downstream from the mutation.
Gene Mutations can Occur Outside of the Coding
Sequence and Influence Gene Expression
A mutation can occur within noncoding sequences,
thereby affecting gene expression (Table 18.2). For
example, a mutation may alter the sequence within the
core promoter of a gene.
The term germ line refers to cells that give rise to the As the embryo grows, this single cell is the
gametes such as egg and sperm. precursor for many cells of the adult
organism. Therefore, in the adult, a portion
of the body contains the mutation.
The size of the affected region
depends on the timing of mutation
(the earlier the mutation – the larger
the affected region)
An example is a path of white hair
18.3 Spontaneous Mutations
Spontaneous mutations result from natural biological and chemical processes, whereas induced mutation are
caused by environmental agents (See Table 18.4)
Three common ways that mutations can arise spontaneously is by depurination, demination, and tautomeric shift
(see Figures 18.7-18.9)
Reactive oxygen species (ROS) can cause spontaneous mutations by oxidizing bases in DNA (see Figure 18.10)
In individuals with a trinucleotide repeat expansion (TNRE) a trinucleotide repeat increases above a certain
critical size end becomes prone to frequent expansion. This type of mutation, called dynamic mutation, is
responsible for certain types of human disease. The repeats can expand due to hairpin formation during DNA
replication (see Table 18.5, Figure 18.11)
Geneticist categorize the cause of mutation in one or two Spontaneous Mutations can Arise by
ways. Depurination, Deamination, and Tautomeric
Shifts
1. Spontaneous Mutations: Changes in DNNA
Depurination: the removal of a purine (adenine or
structure that result from natural biological or
guanine) from the DNA.
chemical processes.
2. Induced Mutations: Caused by environmental o The covalent bond between deoxyribose
agents and purine is unstable and undergoes a
spontaneous reaction with water that
release the base form sugar, creating an
apurinic site.
Instead, if one of the bases is in the enol or imino from, As shown, a thymine base in the template strand has
hydrogen bounding will promote TG and CA base pairs, as undergone a TS prior to the replication, the daughter
shown in Figure 18.9b stand incorporates a guanine opposite this thymine,
creating a base mismatch.
Example:
Com
18.4 Induced Mutations
Nonionizing
UV light
Photolyase is critical for DNA repair enzyme for 1. N-glycosylase recognizes a uracil within the
many plant species (plants are exposed to sunlight) DNA and cleave the bond between the sugar
and bases
Release uracil base and leave behind an
A protein, alkyltransferase (transfers methyl or ethyl from apyrimidinic site
the base to a cysteine side chain) removes methyl or ethyl
groups from guanine bases that have been mutagenized by
alkylating agent such as nitrogen mustard and EMS. (Figure
18.16b)
Uracil
3-methyladenine
7-ethylguanine
4. The final step is carried out by DNA ligase
Thymine dimer
which close a gap in the DNA
Nucleotide excision repair systems remove segments Mismatch repair systems recognize and correct a
of damaged DNA. base pair mismatch
An important process of DNA repair is the nucleotide Another type of abnormality is a base pair mismatch
excision repair (NER) system which repair bulky, helix- (AT/GC rule of base pairing)
distorting lesion.
DNA polymerase has a 3’ to 5’ proofreading ability that
NER can repair: detects mismatches and removes them. If this fails, cells
have additional DNA repair systems such as mismatch
Chemically modified bases
Missing bases repair system that the detect base mismatches and fixes
Crosslinks them.