Changing the Genetic InformationMutations

• A mutation refers to any permanent change in the DNA nucleotide base sequence of an organism.

• Mutations occur spontaneously and randomly throughout the lifetime of all organisms

• The effects of mutations vary depending on their location both within the chromosome (or gene) and the body of the organism.

This red delicious apple illustrates a somatic mutation. A mutation to the ovarian wall gives rise to a sector of yellow colored fruit. The mutation does not affect the seeds (germline) which give rise to the standard red delicious type.

Acquiring Mutations• Mutations in the DNA of an

organism can be caused by:

- Mistakes in DNA replication.• This is a natural process• 1 mistake in 1,000,000,000 bases• Proof reading enzymes correct most

mistakes

- Environmental factors that increase the rate of mutations are called mutagens.

• Radiation• Various chemicals• High temperatures

Can you inherit a mutation?

• Yes! If a mutation occurs in the cells that produce gametes (germ-line cells) the change will be passed onto the offspring.

• If a mutation occurs in any other cell of the body (somatic cells) it will not be inherited, but it may affect the individual during their lifetime.

The biological consequences of mutations

• Mutations may be beneficial, neutral or harmful!

• Mutations are a source of genetic variation – new alleles in a population – that may be selected for by environmental factors and confer an advantage on the organism.

• Mutations are a source of biological novelty for evolution.

Types of Mutations

• Point Mutations (i.e. spelling mistakes)- Changes in a single DNA nucleotide- These can occur within a gene’s coding region or within regulatory

regions of genes

• Block Mutations- Changes in a segment of a chromosome- These changes usually involve the rearrangement of a number of genes

• Chromosome Number Mutations- Changes in the number of chromosomes

A+ A B+ B C+ C D+ D E+ E0

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2

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4

5

6

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TEST AVINDICACTUAL

Point Mutations• Single nucleotide substitutions may result in:1. Changed amino acid sequence2. No amino acid change because genetic code is

degenerate3. Results in “stop” instruction and formation of a new

allele.

Mutation: Substitute T instead of C

OriginalDNA

Mutant DNA

Point MutationsAs a reference for the following screens, the diagram below illustrates the transcription and translation of DNA without a point mutation.

Original Unaltered Code

Transcription

Amino acid sequence forms a normal polypeptide chain

Translation

Original DNA

mRNA

Amino acids

1. Changed amino acid sequence• A single base is substituted by another.

• Usually results in coding for a new amino acid in the polypeptide chain.

Mutation: Substitute T instead of C

Polypeptide chain with wrong amino acid

Original DNA

Mutant DNA

mRNA

Amino acids

2. No amino acid change

A single base is substituted by another.

Called silent or neutral mutations and produce little or no change in the phenotype.

A change in the third base of a codon still codes for the same amino acid.

Normal DNA

mRNA

Amino acids

Amino acid sequence from

the non-mutated DNA forms

a normal polypeptide chain

Mutation: Substitute C instead of T

Mutant DNA

mRNA

Amino acids

Despite the change in the last

base of a triplet, the amino acid

sequence is unchanged

3. Results in “stop” instruction and formation of a new allele

• A single base is substituted by another.

• This results in a new triplet that does not code for an amino acid.

• The resulting triplet may be an instruction to terminate the synthesis of the polypeptide chain.

Mutation: Substitute A instead of C

Original DNA

Mutant DNA

mRNA

Amino acids

Mutated DNA creates a STOP codon which prematurely ends synthesis of the polypeptide chain

Reading Frame Shift by Insertion or DeletionA single base is inserted, upsetting the reading sequence for all those after it.

• A reading frame shift results in new amino acids in the polypeptide chain from the point of insertion onwards.

• The resulting protein will be grossly different from the one originally encoded (it is most likely to be non-functional).

Large scale frame shift results in a new amino acid sequence. The resulting protein is unlikely to have any function.

Mutation: Insertion of C

Original DNA

Mutant DNA

mRNA

Amino acids

Trinucleotide Repeat Expansions

• Many normal human genes contain multiple copies of a three base sequence called a trinucleotide.

• These repeating sequences can expand in number. This mutation gives rise to several inherited conditions.

• The mutant allele that causes “fragile X syndrome” has 200 to 2000 repeats of the trinucleotide CGG, in contrast to 6 to 50 repeats in a normal person, in the untranslated region of the FMR1 gene.

Fragile X Syndrome• Occurs 1 out of every 4000 males and 1 out of

every 6000 females.

• Mutation of the FMR1 gene on the X chromosome leads to loss of the fragile X-metal retardation protein, FMRP. This FMRP protein is involved in the translation of a number of essential neuronal mRNA’s.

• Characteristics of this disease include:- Metal retardation- Shyness and limited eye contact- Elongated face- Large or protruding ears- Large testicles (macroorchidism)- Low muscle tone

Block Mutations• The rearrangement of blocks of

genes within a chromosome. Can occur during crossing over in meiosis

• The rearrangement of blocks of genes between non-homologous chromosomes (translocation). A piece of one chromosome is broken off and joined to another chromosome.

• Block mutations result in a new gene order along a chromosome. They can be highly disruptive!

translocations

Normal

Deletion: Pieces of chromosome are lost.

Duplication: Pieces of chromosome are repeated so there are duplicate segments

Inversion: Pieces of chromosome are flipped so the genes appear in reverse order.

Translocation: Pieces of chromosome are moved from one chromosome onto another.

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• Aneuploidy – changes to the number of specific chromosomes

• Polyploidy- changes to the number of whole sets of chromosomes

Examples of Polyploid Plants

Name Number

Common wheat

6N = 42

Tobacco 4N = 48

Potato 4N = 48

Banana 3N = 27

Boysenberry 7N = 49

Strawberry 8N = 56

Changes to the Chromosome Number

Aneuploidy• Change to the number of specific

chromosomes.

• The extra or missing chromosome may be an autosomal or a sex chromosome.

• Such changes are due to non-disjunctions. These events are due to errors in chromosome segregation in meiosis.

• Pairs of homologous chromosomes may fail to separate in meiosis I or the centromere may fail to separate the sister chromatids in meiosis II.

Down’s SyndromeAn extra chromosome 21

Non-Disjunction: Meiosis INon-disjunction Meiosis I

Meiosis II

n+1 n+1 n–1 n–1Gametes

• A non-disjunction in meiosis I occurs when homologous chromosomes fail to separate properly during anaphase I.

• One gamete receives two of the same sort of chromosome and the other gamete receives no copy.

Non-Disjunction: Meiosis II

• A non-disjunction in meiosis II occurs when sister chromatids fail to separate properly during anaphase II.

• One gamete receives two of the same sort of chromosome and the other gamete receives no copy.

• Some gametes are unaffected.

Meiosis I

Meiosis II

Non-disjunction

n+1 n–1 n nGametes

Turner’s Syndrome 44 + X• Occurs in 1 out of every

25,000 births

• Only one X chromosome is present and is fully functional.

• Common symptoms include:– Short stature– Swelling of hands an feet– Broad chest– Low hairline– Webbed neck

• Occurs in about 1 in 500 to 1000 births.

• Characteristics vary widely.• Males are normally sterile• Some degree of language impairment• Youthful build• Rounded body type• Some degree of gynecomastia• Hypogonadism

Mildly impaired IQ (intelligence)

Poor beard growth

Frequently some breast development (low levels of testosterone)

Chest hair is sparse

Penis and testes underdeveloped, low levels of testosterone. Always infertile.

Female type pubic hair pattern

Limbs tend to be longer than average

Osteoporosis

Sex chromosomes: XXY

Klinefelter’s Syndrome 44 + XXY

Polyploidy

• Organisms that have more than two sets of chromosomes

• Very common in plants because they can reproduce asexually, but rarer in animals.

• Polyploidy can result in “instantaneous speciation”.

• Polyploid plants are usually more robust and sturdy than diploid plants.

• In our long history of plant cultivation we have selected out such plants because they produced a higher yield and were less subject to disease.

• As a result many of our crops today have been bred to a high level of ploidy.

• Wheat was the first crop to be domesticated originating in SW Asia about 10,000 years ago.

• Today, bread wheat is a hexaploid.

An Expert in Polyploidy• The twenty different species

worldwide differ widely in their chromosome number as they exhibit a range of polyploidy.

• The haploid number is 7

• Strawberry species an be:– Diploid– Tetraploid– Hexaploid– Octoploid– decaploid

As a general rule, strawberry species with more sets of chromosomes tend to be more robust and produce larger plants with larger berries.

Fitness of Mutations

• The fitness of a mutation describes its value to

the survival and reproductive success of the

organism. A mutation may turn out to be:

• Lethal: Many mutations are lethal and embryos are non-viable.

• Harmful: Non-lethal mutations, e.g. Down syndrome and sickle cell disease, may be expressed as effects that lower fitness.

• Silent (neutral): Most point mutations are probably harmless, with no noticeable effect on the phenotype.

• Beneficial (useful): Occasionally mutations may be useful, particularly in a new environment, e.g. insecticide resistance in insects, antibiotic resistance in bacteria.

Mutations: Key Points• All new alleles originate by

mutation.

• New alleles introduce genetic variation: the raw material on which natural selection can act.

• Most mutations occur in somatic cells and are not inherited.

• Only mutations in gametes can be inherited.

Evolutionary Significance of Mutations

• Polyploidy can result in the formation of “instant species” by creating a barrier to chromosome pairing at meiosis (common in plants).

• Fusion of chromosomes (a form of translocation) may reduce chromosome number. This can result in reproductive isolation and a new species.

Example: Fusion of chromosomes may have taken place during the course of human evolution.

The chromosome number in the great apes is 2N = 48, whereas in humans 2N = 46.

Human Chimpanzee Gorilla Orangutan

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12

132

1212

11

Possible fusion of two chromosomes to create the No. 2 chromosome in humans.

Note the similar banding patterns of chromosomes from related primate species.