Introduction A mutation is a change in the normal DNA sequence. They are usually neutral, having no effect on the fitness of the organism. Sometimes, beneficial mutations occur, which cause the “mutants” to better survive in their current environment. This is the basis for the theory of Evolution by Natural Selection.

Introduction Mutations are usually thought of as being negative. They are responsible for many disorders. Mutations are caused by mutagenic agents, such as X-Rays, UV radiation, harsh chemicals, etc… which affect/change the nucleotides in DNA.

Point mutations A point mutation is a change in one base in a DNA sequence. Usually occur due to an uncorrected mistake in DNA replication. Often called a substitution mutation because one base pair is switched for another.

Point mutations Transition point mutations exchange a purine for a purine (i.e. A  G) or a pyrimidime for a pyrimidime (i.e. C  T). Transversion point mutations exchange a purine for a pyrimidime or vice versa (i.e. A  C)

Point mutations A point mutation is not a problem if it occurs in an intron section of DNA. However a point mutation in an exon region of DNA may have issues, since these areas of DNA code for protein. When a point mutation in an exon occurs, it falls into one of three categories depending on how it affects the reading frame:

Point mutations 1) Silent Mutation: the change codes for the same amino acid

Point mutations 2) Missense Mutation: the change codes for a different amino acid

Point mutations 3) Nonsense Mutation: the change creates a stop codon.

Frameshift Mutations A frameshift mutation is a mutation that affects how the coding region for a protein is read, and therefore affects the production and structure of that protein. This type of mutation is caused by insertions or deletions.

Insertions An insertion is the addition of nucleotides into the DNA. Can be caused by transposable elements (“jumping genes” as coined by Barbara McClintock---Nobel Prize 1983) which are pieces of DNA that often change their place in the genome throughout the life of the organism. Can be reversed by exonucleases.

Deletions A deletion is the removal of nucleotides from the DNA sequence. These are rarely reversible.

Chromosomal Mutations Mutations can occur on the scale of a chromosome and not just a small sequence of DNA on a chromosome. These mutations are very harmful to the organism.

Chromosome Mutations Both deletions and insertions can happen on the scale of the chromosome. This either removes the genes in those sections (deletions) or affects how they are transcribed/translated (insertions). Sometimes the inserted portion comes from another chromosome.

Chromosome Mutations Chromosomes can also be duplicated, making multiple copies of the same chromosome OR multiple portions of the same chromosome. If this occurred in an egg or sperm cell, disorders like Down Syndrome (Trisomy 21) can occur in the offspring.

Chromosome Mutations A translocation is the trading of chromosomal segments between two different chromosomes. They are usually not the same size segment being traded. Some forms of cancer are caused by translocations (i.e. leukemia).

Chromosome Mutations An inversion is the reversal of a segment of DNA in a chromosome. Since DNA is read in the 5’ to 3’ direction, this can affect protein synthesis as codons will be affected.

Conclusion Mutations are usually neutral and have no effect on the organism. However, when mutations are negative, they can have lethal effects. Point mutations affect one nucleotide and can be silent (no harm), missense (potentially bad) or nonsense (really bad). Frameshift mutations are caused by insertions or deletions of nucleotides and affect the size of the protein which is always bad. Chromosomes can have deletions, insertions, duplications, translocations and inversions… all of which affect protein production and can lead to genetic disorders. Stay away from mutagenic agents as much as possible if you want to minimize your chances of accumulating mutations.