Ch.12 Mutation and DNA Repair Flashcards
Xeroderma pigmentosum
autosomal recessive disorder (1 in 250,000 children). Exposure to UV radiation causes skin cancer. Caused by a loss of function mutation (UV DNA damage repair enzyme is missing)
DNA repair mechanism experience a mutation
Mutation definition
A change in the genetic material, the process by which the change occurs
Mutant
an organism that exhibits a novel phenotype
Mutation
Source of genetic variation
Provides the raw material for natural selection to act upon (no negative or benefit)
Mutation
Source of damage
That contributes to cell death, genetic diseases and cancer.
Mutations have a wild range of effects on organisms depending on?
The type of alteration, the location of the mutation on the chromosome, and the function of the affected gene product.
Types of Mutations
Changes in chromosome number and structure.
Ex: trisomy/monosomy of one chromosomes, breakage and loss of pieces, translocation, inversions.
Point mutations - changes at specific sites in a gene (caused through substitution, insertion, or deletion).
Somatic mutations
In somatic cells; the mutant phenotype will occur only in the descendants of that cell and will not be transmitted to the offspring.
In humans, many kinds of cancers are caused by somatic mutations (skin cancer - through UV damage - that cell divides and all descendants will have cancer. Won’t give cancer to kids)
Germinal mutations
In germ line cells; will be transmitted through the gametes to the offspring.
Dominant mutations: expressed immediately
Recessive mutations: expressed only when they become homozygous in a later generation.
Can occur at any stage of the reproductive cycle (sperm and egg, zygote)
Spontaneous mutations
Occur without a known cause due to inherent metabolic errors, errors during DNA replication or unknown agents in the environment..
Observed frequencies vary by gene and organisms.
Various genes in phages and bacteria 10^8 to 10^10 mutations per nucleotide pair per generation.
In eukaryotes: 10^7 to 10^10 per nucleotide pair per generation.
Mutation rate per gene varies from 10^4 to 10^7 per generation.
Induced mutations
Result from exposure to mutagens, physical and chemical agents that cause changes in DNA, such as ionizing irradiation, ultraviolet light, or certain chemicals.
Treatment with mutagens increases mutation frequencies by orders of magnitudes.
Mutation frequency per gene in bacteria and viruses can be increased to >1%.
The molecular basis of mutation
Mutations may result from:
Single base-pair changes.
Addition or deletion of base pairs (causing frame shift mutations)
Insertion of a transposable genetic element in a gene.
They may also arise when an array of repeated trinucleotides expands.
Single base-pair changes, additions and deletions
Info content can change or info is lost (bc of nonsense results).
Tautomeric shifts
Watson and Crick pointed out that the structure of the DNA bases are not static.
Hydrogen atoms can move and change positions.
Such chemical fluctuations are called tautomeric shifts.
2 diff shifts:
Keto-Enol
Amino-Imino
Tautomeric shifts can result if?
A base exits in the rare form at the moment it is being replicated or being incorporated into the growing DNA chain. Thymine: common keto. rare enol Cytosine: common amino, rare imino Adenine: common amino, rare imino Guanine common keto, rare enol
Tautomeric Shifts affect base-pairing
Hydrogen bonded A:C and G:T base pairs that form when cytosine and guanine are in their rare imino and enol tautomeric forms.
Tautomeric shifts can cause?
Base substitutions
Base substitutions
Transition
Replaces a pyrimidine with another pyrimidine or a purine for another purine.
T and C, C and T (pyrimidine)
A and G, G and A (purine)
Base substitutions
Transversion
Replaces a pyrimidine with a purine or a purine with a pyrimidine. A and T, A and T T and G, G and T G and C, C and G A and C, C and A
Depurination and deamination
Some of the most common causes for?
Mutations
Depurination
Loss of a purine base because glycosidic bond between the deoxyribose and the purine ring breaks
Deamination
(loss of amino group)
Amino group in cytosine or adenine is converted into a keto group; cytosine is converted to uracil, adenine is coverted to hypoxanthine.
Leads to base substitutions
Frameshift mutations
Insertions or deletions of one or more base pairs alter the reading frame of the gene distal to the site of the mutation.
Mutations induced by transposons
Many organisms contain DNA elements that can move from one site to another site.
Insertion of a transposon into a gene will make this gene nonfunctional.
Many classical mutants in maize, Drosophia, E.coli are caused by transposons.
