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
cancer progression
- if additional mutations occur in a benign tumor -> cancer
- malignant-lost normal growth regulation
- invasive- can invade healthy tissue
- metastaic- can migrate to other body parts (via blood vessels)
- left untreated, malignant cells will cause the death of the organism
molecules regulate cell division
- growth factors bind to receptors on the cell wall
- activate signal transducers to relay information
- activate transcription factors to regulate gene activity
in cancer cells..
- receptors may be permanently activated
- signal transducers may be stuck in an activated state
- transcription factors may be produced, even if preceding steps are absent
- apoptosis signals ignored
proto-oncogenes
- regulate cell division by growth factors
- get stuck “on” =ONCOGENE
tumor supressor genes
- stop cell division
- get stuck “off”
- “the accelerator must get stuck and the brakes must fail”
- cancer- from an accumulation of mutations
negative regulator -protein p53
- G1 checkpoint protein
- 50% cancers associated with defect in p53
- p53 expression when DNA is damaged
- resulting protein STOPS cell cycle and REPAIRS damage
- if damage is severe, p53 will activate apoptosis genes
checkpoint genes
- are broken by mutation, the division of normal healthy cells may not be activated
- ex: mice that missing p53 gene born healthy
- cell division leading to normal growth is regulated properly
- checkpoint proteins such as p53 are not necessary for normal cell growth and division
- BUT, highly sensitive to mutagens, easily develop cancer
- loss of checkpoint protein function makes it more likely that genetic changes will occur that could cause cancerous growth
why is cancer rarer among children/ teens/young adults?
??
malignant
(after benign growth) lost normal growth regulation
invasive
can invade healthy tissue
metastatic
can migrate to other body parts
translational response elements (outside gene mutation)
may prevent proper translational regulation
