Chapter 14

Question 1

mutations

Answer 1

• 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

Question 2

gene mutations alter DNA sequence

Answer 2

• point mutations affect only a single base pari
• 2 basic alterations
  1. base substitution
  2. add or remove nucleotides

Question 3

silent mutations (point mutations)

Answer 3

• do not alter AA sequence
• in coding or non-coding region
• genetic code is degenerate (Codon table)
• third base of a codon

Question 4

missense mutation (point mutation)

Answer 4

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

Question 5

nonsense mutation (point mutation)

Answer 5

a normal codon to a stop codon

• shorter polypeptide
• usually bad

Question 6

frameshift mutation (point mutation)

Answer 6

• addition or deletion of nucleotides that are not multiples of 3
• completely different amino acid sequence
• usually VERY BAD; e.g Tay-Sachs disease

Question 7

Promoter mutations

mutation outside coding sequence

Answer 7

-may affect level of transcription

Question 8

Transcriptional response element/ operator site

mutation outside sequence

Answer 8

-may alter regulation of transcription

Question 9

intergenic regions (mutation outside sequence)

Answer 9

typically has little effect on gene expression

Question 10

splice junction (mutation outside sequence)

Answer 10

mutations of intron/ exon boundaries can prevent proper splicing

Question 11

time and location of mutation

Answer 11

determines severity and heritability

Question 12

germ-line cells

Answer 12

• gives rise to gametes

- if a mutated egg or sperm cell participates in fertilization, every cell in the organisms carries the mutation

Question 13

somatic cells

Answer 13

• 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

Question 14

spontaneous mutations

Answer 14

• 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

Question 15

induced mutations

Answer 15

• 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

Question 16

chemical mutagens

Answer 16

• 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

Question 17

physical mutagens

Answer 17

• 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

Question 18

Thymine dimers (Physical mutagens)

Answer 18

• 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

Question 19

Ames test

Answer 19

• 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?

Question 20

DNA repair; two steps

Answer 20

1. proteins detect an irregularity in DNA structure

2. the abnormality is repaired

Question 21

nucleotide excision repair

Answer 21

• 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

Question 22

cancer

Answer 22

• uncontrolled cell division
• 10% inherited; germ-line mutation
• 90%- spontaneous somatic cell mutation

Question 23

carcinogens

Answer 23

• mutagens that increase likelihood of cancer
• 80% of cancers related to mutagens exposure
• change gene expression -> uncontrolled cell division

Question 24

cancer is a series of changes

Answer 24

• usually requires multiple genetic changes

- initially benign tumor, can become malignant with accumulation of more mutations

Question 25

cancer progression

Answer 25

- 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

Question 26

molecules regulate cell division

Answer 26

- growth factors bind to receptors on the cell wall - activate signal transducers to relay information - activate transcription factors to regulate gene activity

Question 27

in cancer cells..

Answer 27

- 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

Question 28

proto-oncogenes

Answer 28

- regulate cell division by growth factors | - get stuck "on" =ONCOGENE

Question 29

tumor supressor genes

Answer 29

- stop cell division - get stuck "off" - "the accelerator must get stuck and the brakes must fail" - cancer- from an accumulation of mutations

Question 30

negative regulator -protein p53

Answer 30

- 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

Question 31

checkpoint genes

Answer 31

- 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

Question 32

why is cancer rarer among children/ teens/young adults?

Answer 32

??

Question 33

malignant

Answer 33

(after benign growth) lost normal growth regulation

Question 34

invasive

Answer 34

can invade healthy tissue

Question 35

metastatic

Answer 35

can migrate to other body parts

Question 36

translational response elements (outside gene mutation)

Answer 36

may prevent proper translational regulation