Chapter 14 Flashcards
mutations
- gene mutation: a small change in the structure of a single gene
- essential to the continuity of life
- source of variation for natural selection
- one way NEW genes can be created!
- -new mutations more likely to be harmful than beneficial
- and are usually random events
- DNA repair systems reverse DNA damage
- cause of many inherited or genetic disorders- cystic fibrosis
gene mutations alter DNA sequence
- point mutations affect only a single base pari
- 2 basic alterations
1. base substitution
2. add or remove nucleotides
silent mutations (point mutations)
- do not alter AA sequence
- in coding or non-coding region
- genetic code is degenerate (Codon table)
- third base of a codon
missense mutation (point mutation)
changes a single amino acid in a polypeptide
- may not alter protein function
- may be neutral if substituted amino acid chemically similar
ex: glutamic acid substituted for aspartic acid - sickle cell anemia
- Glu is hydrophilic, Val is hydrophobic
nonsense mutation (point mutation)
a normal codon to a stop codon
- shorter polypeptide
- usually bad
frameshift mutation (point mutation)
- addition or deletion of nucleotides that are not multiples of 3
- completely different amino acid sequence
- usually VERY BAD; e.g Tay-Sachs disease
Promoter mutations
mutation outside coding sequence
-may affect level of transcription
Transcriptional response element/ operator site
mutation outside sequence
-may alter regulation of transcription
intergenic regions (mutation outside sequence)
typically has little effect on gene expression
splice junction (mutation outside sequence)
mutations of intron/ exon boundaries can prevent proper splicing
time and location of mutation
determines severity and heritability
germ-line cells
- gives rise to gametes
- if a mutated egg or sperm cell participates in fertilization, every cell in the organisms carries the mutation
somatic cells
- all other body cells
- skin, muscle, nerve etc
- mutations can occur early or late in development
- genetic mosaic- patches of mutated tissue
- earlier mutation -> larger affected area
spontaneous mutations
- from abnormal biological process
- rates vary by gene and species
- 1/million genes
- results from:
- erros in DNA replication
- toxic metabolic products
- e.g free radicals
- changes in nucleotide structure
induced mutations
- caused by environmental agent
- mutagens
- higher rate than spontaneous
- brought on by environmental agents
- mutation rate higher than spontaneous mutation rate
- can be both chemical and physical
chemical mutagens
- disrupts DNA base pairing
- modifying nucleotide structure
- nitrous acid (HNO2) deaminates bases by replacing amino groups (-NH2) with keto groups (=O)
- changes C to U and A to hypoxanthine
- bases do not pair correctly; results in leads to point mutations
physical mutagens
- ionizing radiation has high energy and can penetrate deeply into biological materials to create free radicals
- X rays and gamma rays
- base deletions, breaks DNA strands, free radical generation
- non ionizing radiation has less energy and can only penetrate the surface (skin-deep)
- UV rays can cause formation of thymine dimers
Thymine dimers (Physical mutagens)
- can result in replication issues:
- DNA polymerase misreads
- proper nucleotides are NOT added to the new DNA strand
- can cause gaps in the new DNA
- can cause wrong bases to be incorporated
Ames test
- to determine mutagenicity of chemicals
- uses a mutant strain of the bacterium of Salmonella typhimurium
- this strain cannot synthesize histidine
- a SECOND mutation in the cell can correct the FIRST
- test monitors the rate at which second mutation occurs
- does an agent increase mutation rate above the spontaneous rate?
DNA repair; two steps
- proteins detect an irregularity in DNA structure
2. the abnormality is repaired
nucleotide excision repair
- referred to as the NER system
- a region of several nucleotides around damaged base is removed and replaced
- deficiency in NER system can have serious consequences
cancer
- uncontrolled cell division
- 10% inherited; germ-line mutation
- 90%- spontaneous somatic cell mutation
carcinogens
- mutagens that increase likelihood of cancer
- 80% of cancers related to mutagens exposure
- change gene expression -> uncontrolled cell division
cancer is a series of changes
- usually requires multiple genetic changes
- initially benign tumor, can become malignant with accumulation of more mutations