Mutations

A mutation is a change in the normal DNA sequence.

They are usually neutral, having no effect on the fitness of the organism.

General types of Mutations

Introduction

Or they are harmful, and are responsible for many disorders.

General types of Mutations

Sometimes, beneficial mutations occur, which cause the “mutants” to better survive in their environment.

These mutations lead to adaptations and are the basis for the theory of Evolution by Natural Selection.

There are 2 General Categories of Mutations

Single gene Mutations

Changes in nucleotide sequence of one-gene

Chromosomal Mutations

Changes in chromosomes, involve many genes

Types of Single Gene Mutations

A) Point mutations

a change in one nucleotide OR base pair in a gene

Often involves a substitution mutation where one base pair is switched for another.

Can also be a single base pair insertion or deletion.

Usually occur due to an uncorrected mistake in DNA replication.

Insertions can be fixed by exonucleases.

Deletions are rarely reversible.

Substitutions, Insertions and Deletions

A point mutation is not a problem if it occurs in an intron section of DNA.

A point mutation may cause problems if it occurs in an exon region of DNA , since these areas of DNA code for protein.

The effects of Point mutations on Protein

Insertion and Deletion mutations (but NOT substitution mutations) can result in frameshift mutations.

If a number of nucleotides is added or removed that is not a factor of 3 this causes the entire reading frame of the gene to be altered.

Frameshift Mutation

Analogy: THE CAT ATE THE RAT - delete C THE ATA TET HER AT - no longer makes

sense

THE CAT ATE THE RAT - add BAD THE BAD CAT ATE THE RAT - still makes

sense

Frameshift Mutations

Frameshift Mutations

There are 3 main categories for how mutations affect the amino acid sequence of the protein:

The effects of mutations on Protein

1) Silent Mutations

Due to the redundant nature of the genetic code the mutation codes for the same amino acid

2) Missense mutations

the mutation codes for a different amino acid

Can be harmful, for example alkaptonuria- most often due to a substitution mutation leading to a missense mutation.

Alters the gene for the enzyme that degrades tyrosine ;

Due to the faulty enzyme, homogentisic acid accumulates in the body, causes black urine damages cartilage &heart valves, causes kidney stones

Missense Mutation Examples

Sickle Cell Anemia is another disease caused by a single base pair substitution leading to a missense mutation.

Missense Mutation Examples

Missense Mutations can also be beneficial and may play a role in creating new proteins, such as antibodies, for fighting new infections.

Missense Mutation Examples

3) Nonsense Mutations

the change results in a premature stop codon.

Can be lethal to the cell, usually very harmful to the organism.

Nonsense Mutations

Change to the chromosome number is always detrimental, if not lethal, to the organism

Chromosomal Mutations

Chromosomal Mutations

Mutations can also involve rearrangement of genetic material which may affect several genes and several chromosomes and therefore protein synthesis.

Chromosomal Deletions and Duplications

Deletions result in a loss of genes

Duplications result in multiple copies of genes or even chromosomes.

Inversions

An inversion is the reversal of a segment of DNA in a chromosome.

Translocations

A translocation is the trading of chromosomal segments between two different chromosomes.

Translocations

They are usually not the same size segment being traded.

Some forms of cancer are caused by translocations (i.e. leukemia).

Spontaneous mutations occur naturally

Induced mutations are caused by environmental factors.

Causes of Spontaneous mutations include:Errors in DNA replicationDNA transposition

CAUSES OF MUTATIONS

movement of specific DNA sequences, called transposable elements, or transposons, within and between chromosomes.Described by Barbara McClintock (American geneticist) 1949.

DNA Transposition

A mutagen or mutagenic agent is a substance or event that increases the rate of mutation.

Causes of Induced mutations

cause physical damage to DNA X-Rays – point mutations and

chromosomal deletions UV radiation – causes

reactions between adjacent pyrimidine bases (C and T)

Physical Mutagens

Chemical mutagens react chemically with DNA to cause a nucleotide substitution or frameshift mutation.

May also have a similar structure to a nucleotide but with different base pairing properties

Chemical Mutagens

Nitrites (small amounts in cured meats)

Gasoline fumes50+ compounds found in cigarette smoke

Most chemical mutagens are also carcinogenic

Examples of Chemical Mutagens

Mutations that accumulate too rapidly or are very harmful do not provide a selective advantage.

The DNA polymerase enzymes can repair errors made in DNA replication.

DNA Repair

Mismatch repair by Mut proteins also helps to reduced replication errors.

Cells have other mechanisms that recognize and repair DNA that becomes damaged.

DNA Repair

Photorepair is used to correct UV radiation damage. A photolyase enzyme uses visible light to cleave the bond made between adjacent pyrimidines.

Excision repair enzymes recognize and remove many different forms of damage, a DNA polymerase enzymes rebuild the removed segment.

Examples of DNA Repair

Mutations are usually _______________and have no effect on the organism.

However, when mutations are _____________, they can have lethal effects.

_____________ mutations are rare and result in ____________________.

Conclusion

_______________________affect one nucleotide

_______________________are caused by insertions or deletions of nucleotides.

The result of a mutation on the protein is considered __________ (no effect), _____________ (single amino acid change) or ______________ (premature stop codon).

Conclusion

Chromosomes can have _______________, ___________________, _______________, and ___________________… all of which affect protein production and can lead to genetic disorders.

Stay away from _____________________as much as possible if you want to minimize your chances of accumulating mutations.

Conclusion