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Chapter 5

BCH447H1 Chapter Notes - Chapter 5: Vernon Ingram, Silent Mutation, Sickle-Cell Disease

Course Code
Peter Hyland

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Chapter 5: Mutation and Genetic Variation (pages 143 – 163)
The genetic variation that natural selection and other evolutionary forces act on
originates in mutation. Meiosis can be responsible for this because of the crossing
over process can result in new grouping of alleles. However, meiosis reshuffles
existing alleles into new combinations. Therefore, only mutation can create new
alleles and new genes. Once this variation is produce, then selection, drift, and
migration can act.
5.1. Where New Alleles Come From
The Nature of Mutation
oMutation is any change in DNA. Genes are made of DNA, so changes in
DNA create changes in genes
oConsider the mutation for the human gene for hemoglobin that results in
In 1958, Vernon Ingram showed that the difference between
normal and sickle-cell hemoglobin was due to a single amino acid
change at position number 6 in the protein chain.
Instead of having glutamic acid in this position, the sickle cell
allele has valine; caused by a single base substitution in the
hemoglobin gene.
A change like this is called a point mutation which is a change in a
single base pair in DNA and occurs when errors in DNA replication
or repair are not fixed properly.
oPoint mutations are caused by one of two processes:
Random errors in DNA synthesis
Random errors in the repair of sites damaged by chemical
mutagens or high-energy radiation
oIf DNA polymerase mistakenly substitutes a purine for another purine or
a pyrimidine for another, the resulting point mutation is known as
oIf a purine is substituted for a pyrimidine or a pyrimidine for a purine,
the mutation that results is called a transversion.
Transitions are most common
oChanges in the first or second position of a codon almost always change
the amino acid specified by the resulting mRNA; however, due to the
redundancy of the genetic code, changes in the third position frequently
produce no change at all.
Point mutations that results in an amino acid change are called
replacement substitutions.
Those that result in no change in the amino acid coded are silent
site substitutions
Both types result in new alleles
Mutation Rates
oRead about this research done on page 148
oThe research suggests that the mutation rate per cell divisions is
approximately equal in most or all organisms
oSuggested that natural selection had led to a single, common mutation
oRead about Recent Work on pages 148 – 149 (insignificant material)
Early results suggest that mutation rates may exceed two new
mutations per individual per generation and vary among
population and species
Mutation rates vary due to variation in the structure of enzymes
involved in DNA replication and repair. High mutation rates may
be selectively advantageous in novel or rapidly changing
The Fitness Effects of Mutations
oRead page 150 (no need to memorize the material; just read it)
The vast majority of mutations reduce fitness slightly or are
neutral (e.g. silent mutation) with respect to fitness
5.2 Where New Genes Come From
Gene mutations are probably the most important source of new genes. Most
duplications result from one of two processes:
Retrotransposition – the process begins when a processed messenger
RNA (lacks introns but has a poly [A] tail), is reverse-transcribed by the
enzyme reverse transcriptase to form a double stranded segment of
Unequal Crosser – this is more common. It is a chance mistake caused
by the proteins involved in managing the genetic recombination that
occurs during meiosis.
oSee Fig. 5.6 on page 153
oBegins when homologous chromosomes do not synapse correctly
during prophase of meiosis I.
Results in one chromosome that contains a deletion and
one that contains a redundant stretch of DNA
Rates of Gene Duplication
oEstimates suggest that the average rate of genes that duplicate
and increase to high frequency in populations at 0.01 per gene
per million years.
This means that in species with a genome containing 10
000 genes, a gene is duplicated and increases to high
frequency every 10 000 years on average
The Fate of Duplicated Genes
oWhen DNA sequences are duplicated via retrotransposition or
unequal cross-over, the original gene should continue to produce
a normal product
oThe duplicated sequences are redundant and may accumulate
mutations without consequences to the phenotype
This may even change function and become an entirely
new gene instead of a copy of an existing gene.
Read page 154 for an example
oDuplicated genes can retain their original function and provide an
additional copy of the parent gene, gain a new function through
mutation and selection, or become functionless pseudogenes
oRegardless of the function of a duplicated gene, they are
homologous with respect to each other because they are derived
from the same common ancestral sequence
Homologous genes come in two types
Genes that are duplicated and then diverge in
sequence are said to be paralogous
Homologs found in different species are said to be
5.3 Chromosome Mutations
oOften result from a multistep process that starts when radiation causes
two double-strand breaks in a chromosome.
After a breakage, the chromosome segment can detach, flip, and
reanneal in its original location (Fig. 5.9).
In addition to involving much larger stretches of DNA that point
mutation and gene duplications, inversions produce very different
Affect a phenomenon known as genetic linkage
oLinkage is the tendency for alleles of different genes
to assort together at meiosis
oRead example of the fly on page 157
Inversions change gene order and lessen the frequency of
crossing over between homologous segments of chromosomes.
As a result the alleles inside inversions tend to be inherited.
Inversion are an important class of mutations because they affect
selection on groups of alleles
Genome Duplication
oOccurs at the largest scale possible; entire sets of chromosomes
For example: if homologous chromosomes fail to segregate during
meiosis I or if sister chormatids do not separate properly during
meiosis II, the resulting cells may have double the chromosomes
of the parent cell
Mutations like these can lead to the formation of a diploid gamete
in species where gametes are normally haploid
oOrganisms that have more than two chromosome sets are said to be
This is common in plants, but rare in animals
In animals, this occurs in taxa such as earthworms and flatworms
where individuals contain both male and female gonads and can
Polyploidy and Speciation
oPolyploid individuals may represent a new species, because it is difficult
for them to breed with individuals from the original population
When triploid individuals breed with the original population, their
gametes cannot synapse correctly because they are present in an
odd number (e.g. 3n)
Triploid individuals have extremely low fertility