mutation Flashcards
Mutation
The alteration of a sequence of nucleotides in DNA, that may change the RNA product.
Carcinogenic mutagens
Mutagens that change the cell cycle, causing increased cell division with no differentiation and creating masses of cells known as tumours.
What mutations cause cancer?
Mutations in proto-oncogenes and tumour suppressor genes.
Electromagnetic radiation sources
Enter cells from external sources and interfere with DNA molecules in the nucleus due to its highly-penetrative high-energy waves.
Ex. gamma rays, x-rays and UV light
Pyrimidine dimers
UV creates a dimer structure by causing two adjacent base pairs to form covalent bonds with each other.
Why are pyrimidine dimers bad?
They distort DNA’s double helix structure and prevent T bases form bonding with the opposite A bases.
The dimer structure isn’t replicated by DNA polymerase so no nucleotides are paired with the covalent pair, altering the mRNA sequence and negatively affecting protein structure/protein function.
How else may radiation indirectly damage DNA?
By ionising other molecules to produce highly-reactive free radicals.
These unpaired electrons want to strip electrons from any molecules they encounter, reacting with DNA to damage it.
Examples of chemical mutagens
Ingested chemicals like alcohol, charred and fatty foods. Environmental irritants and poisons like asbestos and pesticides.
Base analogues
Chemicals structured similar to normal bases in DNA and may mistakenly become incorporated into DNA during replication. Results in mispairing of nucleotides, creating a non-functional protein product.
Intercalating agents
Chemicals that insert themselves into the bonds between DNA pairs, altering the shape of DNA. Causes errors in replication.
Reactive oxygen species
Chemicals that react directly with DNA and can cause breakages and cross-links in DNA strands.
Naturally occurring mutagens
Spontaneous mutations like DNA replication errors that are retained because normal DNA repair doesn’t correct them
Non biological naturally occurring mutagens
Metals like mercury and cadmium that occur naturally in the environment
Biological naturally occurring mutagens
Viruses, bacteria, fungi and their products.
Mutagenic microbes can insert their own base sequence into DNA, changing the functioning of genes and triggering cancer.
Transposons
Sections of DNA that spontaneously fragment and relocate or multiply within the genome.
When inserted into chromosomal DNA, they disrupt DNA functioning.
Microbes
Mutagens such as viruses (HIV, hep B) and bacteria (Helicobacter) that may alter the genetic material in cells.
Point mutation
A single nucleotide variation. Different from SNPs because they exist in less than 1% of the species’ population.
Effects of point mutation
Affects phenotype if they occur within the exon of a gene, or affects gene expression when occurring within an intron.
Base substitution
When one nucleotide base is replaces by a different base, possibly leading to a different amino acid inserted in the polypeptide.
Nonsense mutation
Amino acid is changed into a premature stop codon, resulting in a non-functional resulting protein that has major phenotypic effect.
Missense mutation
Results in an amino acid change. Functionality of the resulting protein is determined by whether the replacement amino acid is the same as the original.
Silent mutation
When a substitution results in a new codon that still codes for the same amino acid, and thus have no effect on proteins and phenotype. Doesn’t alter amino acid sequence.
Neutral mutation
Changes in DNA that result in an amino acid of the same type as the original so the change doesn’t significantly affect the structure of the protein.
Sickle cell anaemia
A missense mutation; the amino acid glutamate is swapped for valine, altering the shape of the haemoglobin molecule and resulting in the sickle cell shape of the red blood cells.
Insertions and deletions
The entire ‘reading frame’ of RNA is shifted, affecting every RNA codon after the change and impacting the production of the polypeptide. –> Frameshift mutation
Effects of insertions or deletions
The polypeptide can be interrupted or not produced at all if one of the resulting codons is a stop codon. Ex. Muscular dystrophy
Chromosomal mutation
Large-scale changes of DNA within a chromosome.
Chromosomal deletion
When a section of DNA is removed and not replaced, leading to a reduction in the number of genes in a chromosome.
Chromosomal insertion (duplication)
When a portion of DNA is duplicated and inserted. Effects depend on the size, location and number of repeats.
Chromosomal inversion
When a section of DNA is removed, turned 180º and reinserted into the chromosome so that the bases are in reverse order. Ex. Haemophilia A, caused by an inversion mutation in the factor VII gene on the X chromosome.
Chromosomal translocation
When a section of DNA is moved from one chromosome to a non-homologous chromosome. May lead to gene fusion, when the translocated region joins two normally separated genes.
Aneuploidy
Numerical change in part of the chromosome set. Ex. Down syndrome
Polyploidy
A numerical change in the whole set of chromosomes, resulting from all homologous chromosomes not separating during meiosis with one gamete having (2n) chromosomes and the others having none. Common in plants like tulips.
Somatic mutations
Occurs in somatic cells (cells in the body other than sex organs), often due to replication errors prior to mitosis. Not hereditary, so no impact on species and their evolution. Ex. melanoma due to exposure to UV rays.
How does a somatic mutation spread?
When a mutated cell continues to divide by mitosis, the error is replicated each time and passed onto cells in successive divisions, amplifying the error within that tissue. This may result in an observable phenotypic difference in the tissue such as cancer.
Germline mutations
Occurs in the sexual reproductive cells that give rise to gametes and these mutations are passed to offspring. Can contribute to the species’ gene pool and influence whole populations of organisms and their evolution.
How are germline mutations passed on?
When an affected gamete fuses with another and forms an embryo, the mutation is replicated in every cell of the embryo as it divides and grows, affecting all cells in the resulting child.
Example of germline mutation in terms of meiosis
Homologous chromosomes in meiosis 1 or sister chromatids in meiosis 2 fail to separate correctly –> one gamete will end up with 2 copies of one chromosome, and another will end up without any copies of that chromosome.
Coding DNA
Affects the type or sequence of amino acids in a protein end-product. As proteins are the product of genes in the coding region of DNA, if a mutation occurs, it directly affects the protein and the phenotype of the individual.
How do coding DNA mutations affect eukaryotes?
May affect gene splicing and modify the function or levels of the protein product. The result of errors in eukaryotic genes involved in DNA repair are a general increase in mutations.
How do coding DNA mutations affect prokaryotes?
Prokaryotic DNA is mostly coding DNA, so maintaining the integrity of DNA is essential for the survival of these species. Characteristics for DNA repair enzymes are not tolerant of genetic variation and change.
Non-coding DNA
Mutations in these non-coding regions (regulatory sequences) affect gene expression and cell functioning.
What is the significance of non-coding DNA in embryonic development?
Non-coding DNA is important during embryonic development, showing a link to birth defects. They may lead to developmental abnormalities that cause the embryo or foetus to be aborted, or may lead to congenital abnormalities.
What evolutionary advantage is non-coding DNA suggested to provide?
Acts as a buffer area dividing one gene from the next. If a frameshift mutation arises, the introns will minimise the changes caused by the mutation. Gives leeway when genes break during crossing over, so the recombination doesn’t have to have pinpoint accuracy.
