Lecture 2: Mutations: the source of Mutation

variation
Locus ≈ gene = a physical position on a
Today’s topics: chromosome
1. Point mutations Locus and gene are often used interchangeably.
2. Insertions and deletions “Gene” is used more often by non-geneticists.
3. Chromosomal mutations
4. Recombination Mutation = change in genetic information that is
passed on to other cells

Mutations can have minor or severe effects on the

phenotype.

Mutation “Random” mutations?

Germ-line mutations are passed on to the
offspring. Mutations do not occur because an organism
“needs” the mutation.
(Somatic mutations are not.)
The mutation occurs first, then the organisms which
possess the mutation have better (or worse)
survival/reproduction.

“Spontaneous” may be a better descriptor than

“random”.

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 Point mutations Point mutations
The simplest mutation is a point mutation There is now a new allele.
(= base substitution = single nucleotide
Allele: one particular form of a gene
substitution).
(many alleles typically exist in a species)

Point mutations Point mutations

When multiple alleles coexist within a species - the oval represents a population
- letters represent the nucleotide at a base pair position
at the same time, the locus or base pair site
- each letter is a different allele on a different chromosome
is polymorphic. copy

(A base pair position or locus with no A A AA A G AA G G AG G G GG

variation is monomorphic.) AA A A AA A A GA A G GG G G

monomorphic polymorphic polymorphic monomorphic

The population is
--> Time --> now "fixed" for G
at this base pair
position

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 Mutation Point mutations
Geneticists traditionally used the term Polymorphic point mutation sites are called SNPs
"wild type" to mean the most common phenotype (Single Nucleotide Polymorphisms)
or allele in nature.
SNPs are becoming easier and cheaper to screen
Alternative forms have been called "mutants". for diseases, etc.

Mendel called
different
phenotypes
"variations".

Point mutations Point mutations

For reasons of efficiency and a better understanding T and C are pyrimidine bases
of mechanisms, it is usually better to know the A and G are purine bases.
composition of the haplotypes than simply the SNPs.
T <-> C and A <-> G mutations are called
transition mutations.

www.hapmap.org

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 Point mutations Point mutations
T <-> C and A <-> G mutations are called Twice as many transversions as transitions are possible.
transition mutations. But if we compare evolutionary changes between species,
T <-> A , T <-> G , C <-> G and C <-> A transitions are more common!
mutations are called transversion mutations. Why?

Point mutations Point mutations

Why are transitions more common than transversions? Mutations that have no effect on amino acid
One reason: the genetic code is redundant, and transitions composition are silent (or synonymous) mutations.
are less likely to cause an amino acid change.

T (or U) <-> C and A <-> G are transitions

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 Point mutations Point mutations
Nonsense mutations create a new stop codon. Missense (or nonsynonymous or replacement)
mutations change amino acids.

Point mutations Sickle-cell anemia

Example of nonsynonymous mutation:
sickle-cell anemia

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 Phenylketonuria (PKU) Insertions and deletions
PKU is caused by a The insertion or deletion
point mutation in
the phenylalanine
of a base causes a “frame
hydroxylase gene. shift”.
The reading frame will
Originally change for every codon
ATGTCC... downstream from the
mutation.

Chromosomal mutations Chromosomal rearrangements

Chromosomal mutations involve portions of genes, Chromosomal rearrangements change the
entire groups of genes, or even entire structure of one chromosome.
chromosomes.
1. Duplication
(Rarely, one or more genes may be deleted or • Tandem duplication: duplication is
inserted by a number of mechanisms.) adjacent

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 Tandem duplications Tandem duplications
The “motif” for a tandem duplication is a piece of DNA Unequal crossing over can cause a tandem duplication.
at least 2 bp long.
...TCG ATC ATC ATC ATC GAC...
4 repeats Example: some kinds of red-
green color blindness
These types of polymorphisms are also called:
- SSR (Simple Sequence Repeat)
- “microsatellite”: usually < 10 bp motif
- “minisatellite”: 10-60 bp motif

Tandem duplications
Gel electrophoresis separates DNA fragments of different sizes
using electricity.
DNA fingerprinting usually means the separation of different
microsatellite alleles.

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 Chromosomal rearrangements Chromosomal rearrangements
1. Duplication 1. Duplication
• Tandem duplication: duplication is adjacent • Tandem duplication: duplication is adjacent
• Displaced duplication: duplication is not • Displaced duplication: duplication is not
adjacent adjacent
-> may be on the same chromosome or a different -> may be on the same or different chromosomes
chromosome

Tandem
duplication

Chromosomal rearrangements Chromosomal rearrangements

1. Duplication 2. Deletion
• Tandem duplication: duplication is adjacent
• Displaced duplication: duplication is not
adjacent
• Reverse duplication: duplication is inverted

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 Chromosomal rearrangements Chromosomal rearrangements
2. Deletion Pericentric inversion in human chromosome 4.
3. Inversion order for a gene or
group of genes is reversed
• Paracentric inversion
does not include the centromere

• Pericentric inversion • Pericentric inversion

includes the centromere includes the centromere

Recall from introductory biology: Chromosomal rearrangements

Homologous (same) chromatids align at metaphase plate
If the population is polymorphic for a chromosomal duplication,
during meiosis, and sometimes there is recombination. deletion or inversion, then some individuals will have one version
of each chromosome type.
In these individuals, chromosome loops are formed during cell
division to maintain gene-for-gene attraction.

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 Chromosomal rearrangements
If there are no crossovers in these loops, there are no
structural problems during chromosome separation.

Inversion loops Chromosomal rearrangements

If there is a crossover in an inversion loop, only 2 of the 4 chromatids
will get the correct set of genes.
4. Translocations
• Reciprocal translocation
The other chromatids cannot successfully Two chromosomes exchange genes (Fig. 9.5)
form a zygote.
No recombinant • Nonreciprocal translocation
chromosomes Genes move from one chromosome to another
will be found in • Roberstonian translocation
the offspring … Break point close to the centromere creates a
even if there new very long chromosome (Fig. 9.16)
were crossovers!

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 Chromosomal rearrangements Chromosomal rearrangements
Reciprocal translocation between chromsomes 9 and 22 Robertsonian translocation in human chromosome 2.
causes chronic myelogenous leukemia.

Change in chromosome number Change in chromosome number

In addition to changes in chromosome content, the
number of chromosomes might change through
mistakes in meiosis or mitosis.
1. Aneuploidy: change in the number of individual
chromosomes
2. Polyploidy: change in the number of chromosome
sets.
Trisomy for chromosome 21
causes Down syndrome

Trisomies for different

chromosomes in Jimson weed
produce different capsule shapes.

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 Change in chromosome number Polypoidy can form new species

Recombination Recombination
If recombination occurs within a gene, it will
often produce a new allele.

Therefore, recombination is similar to

mutation.

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