Genetic Mutation

A Permanent Change in the

Nucleotide Sequence of

the Genome of an Organism

In genetics, a mutation is a change of the nucleotide sequence of

the genome of an organism, virus, or extra chromosomal genetic

element.

Mutations result from unrepaired damage to DNA or to RNA

genomes, errors in the process of replication, or from the insertion

or deletion of segments of DNA by mobile genetic elements.

Mutations play a part in both normal and abnormal biological

processes including: evolution, cancer, and the development of the

immune system.

Genetic Mutation:

A change in the genetic structure that is not inherited from

a parent, and also not passed to offspring

Not present in the germ-line of the organism

Will change the phenotype of the individual containing it

If occurs early during organismal development, will likely

be in many cells, seeming as though the mutation exists in

the entire organism

If occurs later during organismal development, may only

be in a few cells within the organism.

Acquired Mutation:

Somatic Mutation:

Any detectable and heritable variation in the lineage of germ

cells.

Exists or has occurred in the sperm or egg and is passed to the

progeny.

Can occur during early embryonic development when the

embryo is made up of only a few cells.

Would be present in almost all of the resulting organism's cells.

Germline Mutation:

Germinal Mutation:

By Effect on Structure:

Classification of Mutation Types:

Point mutations, often caused by chemicals or malfunction of DNA replication,

exchange a single nucleotide for another (e.g., conversion of adenine [A] into

a cytosine [C]).

Insertions, add one or more extra nucleotides into the DNA. They are usually

caused by transposable elements, or errors during replication of repeating

elements (e.g., AT repeats).

Deletions, remove one or more nucleotides from the DNA. In general, they are

irreversible.

Amplifications(or gene duplications), leading to multiple copies of all

chromosomal regions, increasing the dosage of the genes located within them.

Loss of heterozygosity: loss of one allele, either by a deletion or

a recombination event, in an organism that previously had two different alleles.

Amorphic mutation, result in the gene product having less or no function. When

the allele has a complete loss of function (null allele) it is often called an Loss-

of-function mutations.

Aneomorphic mutation, change the gene product such that it gains a new and

abnormal function. These mutations usually have dominant phenotypes. Often

called Gain-of-function mutations.

Antimorphic mutations, have an altered gene product that acts antagonistically

to the wild-type allele. These mutations usually result in an altered molecular

function (often inactive) and are characterized by a dominant or semi-

dominant phenotype, also called as Dominant negative mutations. In humans,

dominant negative mutations have been implicated in cancer

Lethal mutations, are mutations that lead to the death of the organisms that

carry the mutations.

A back mutation or reversion is a point mutation that restores the original

sequence and hence the original phenotype

By Effect on Function:

Frameshift mutation, is a mutation caused by insertion or deletion of a number of

nucleotides that is not evenly divisible by three from a DNA sequence.

Non-sense mutation, is a point mutation in a sequence of DNA that results in a

premature stop codon, or a nonsense codon in the transcribed mRNA, and often non-

functional protein product.

Missense mutations or non-synonymous mutations, are types of point

mutations where a single nucleotide is changed to cause substitution of a different

amino acid. Such mutations are responsible for diseases such as sickle-cell disease.

Neutral mutation, is a mutation that occurs in an amino acid codon that results in the

use of a different, but chemically similar, amino acid. The similarity between the two

is enough that little or no change is often rendered in the protein. e.g., a change from

AAA to AGA will encode arginine, a chemically similar molecule to the

intendedlysine.

Silent mutations, are mutations that do not result in a change to the amino acid

sequence of a protein, unless the changed amino acid is sufficiently similar to the

original. They may occur in a region that does not code for a protein

By Impact on Protein Sequence:

A heterozygous mutation is a

mutation of only one allele.

A homozygous mutation is an

identical mutation of both the

paternal and maternal alleles.

Compound

heterozygous mutations or

a genetic compound comprises

two different mutations in the

paternal and maternal alleles.

By Inheritance:

A mutation has caused this gardenmoss rose to

produce flowers of different colors. This is a somatic

mutation that may also be passed on in the germ line.

Spontaneous mutations on the molecular level can be caused by:

Tautomerism — A base is changed by the repositioning of a hydrogen atom,

altering the hydrogen bonding pattern of that base, resulting in incorrect

base pairing during replication.

Depurination — Loss of a purine base (A or G) to form an apurinic site.

Deamination — Hydrolysis changes a normal base to an atypical base

containing a keto-group in place of the original amine group. Examples

include C → U, which can be corrected by DNA repair mechanisms.

Slipped strand mispairing — Denaturation of the new strand from the

template during replication, followed by renaturation in a different spot. This

can lead to insertions or deletions.

Spontaneous Mutation

Causes of Mutation:

Majority of spontaneously arising mutations are due to error

prone replication past a DNA damage in the template strand.

Naturally occurring DNA damages arise about 60,000 to

100,000 times per day per mammalian cell.

Error Prone Replication By-Pass:

A Non-homologous end joining is

a major pathway for repairing

double-strand of DNA breaks.

NHEJ involves removal of a few

nucleotides to allow inaccurate

rejoining of the two ends.

It followed by addition of

nucleotides to fill in gaps.

As a result, NHEJ often

introduces mutations.

Errors Introduced During DNA Repair:

Induced mutations on the molecular level can be caused by:-

Chemicals

DNA intercalating agents (e.g., ethidium bromide)

DNA cross linkers

Oxidative damage

Base analogs (e.g., BrdU) etc.

Radiation

Two nucleotide bases in DNA (cytosine and thymine) are most sensitive to

ultraviolet radiation that can change their properties.

Ultraviolet radiation, in particular longer-wave UVA, can also

cause oxidative damage to DNA.

Induced Mutation:

Cancer tumors are a unique class of somatic mutations.

Cancer results when cells accumulate genetic errors and multiply

without control.

The tumor arises when a gene involved in cell division is mutated.

All of the daughter cells contain this mutation.

The phenotype of all cells containing the mutation is uncontrolled

cell division. This results in a collection of undifferentiated cells

called Cancer cells.

Usually, it takes multiple mutations over a lifetime to cause cancer.

Mutation and Cancer:

Examples of Cancer in Plants: