Mutations

General types of Mutations A mutation is a change in the normal DNA sequence. They are usually neutral, having no effect on the fitness of the organism.

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.

Substitutions, Insertions and Deletions Usually occur due to an uncorrected mistake in DNA replication. Insertions can be fixed by exonucleases. Deletions are rarely reversible.

The effects of Point mutations on Protein 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.

Frameshift Mutation 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 Mutations 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

The effects of mutations on Protein There are 3 main categories for how mutations affect the amino acid sequence of the 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

Missense Mutation Examples 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.

3) Nonsense Mutations the change results in a premature stop codon.

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

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

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).

CAUSES OF MUTATIONS Spontaneous mutations occur naturally Induced mutations are caused by environmental factors. Causes of Spontaneous mutations include: Errors in DNA replication DNA transposition

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

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

Physical Mutagens cause physical damage to DNA X-Rays – point mutations and chromosomal deletions UV radiation – causes reactions between adjacent pyrimidine bases (C and T)

Chemical 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

Examples of Chemical Mutagens Nitrites (small amounts in cured meats) Gasoline fumes 50+ compounds found in cigarette smoke Most chemical mutagens are also carcinogenic

DNA Repair 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.

Examples of 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.

Conclusion 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.