Chapter 14

Question 1

Intro

Answer 1

DNA stores, replicates, transmits and decodes info
Change in DNA seq give rise to variation
- result in phenotypic variability, adaptation to
environmental changes and evolution
Gene mutations
- new source of alleles and genetic variation in population
- source of genetic changes that can lead to cell death,
genetic disease and cancer.

Question 2

Mutations

Answer 2

• Alteration in DNA sequence
• Any bp change in sequence
• Single bp substitution
• Deletion of insertion of bp
• major alteration in chromosomal structure
  may occur in somatic or germ cells
  may occur in coding of noncoddoing region

Question 3

Mutation classification by molecular change

Answer 3

• Point mutation or base substitution: change from one base pair to another
• Missense mutation: results in new triplet code for different amino acid
• Nonsense mutation: results in triplet code for stop codon (translation terminated prematurely)
• Silent mutation: New triplet code still codes for same amino acid.

Question 4

Base substitutions (Point Mutations)

Answer 4

• Transitions: Pyrimidine replaces pyrimidine, or purine replaces purine.
• Transversions: Purine and pyrimidine are interchanged.
• AG (purine) CT (pyrimidines)

Question 5

Frameshift mutations

Answer 5

• Result from insertions or deletions of base pair
• Loss or addition of nucleotide causes shift in reading frame
• Frame of triplet reading during translation is altered

Question 6

Mutations classified by phenotype

Answer 6

1. Loss-of-function mutations
2. Gain-of-function mutations
3. Visible (morphological) mutations
4. Nutritional (biochemical) mutations
5. Behavioral mutations
6. Regulatory mutations
7. Lethal mutations
8. Conditional/temperature-sensitive mutations

Question 7

Loss-of-function mutation

Answer 7

reduces/eliminates function of gene product

Question 8

Null mutation

Answer 8

results in complete loss of function

Question 9

Dominant mutation

Answer 9

results in mutant phenotype in diploid organism

Question 10

Dominant gain-of-function mutation

Answer 10

results in gene with enhanced, negative, or new function

Question 11

Visible (morphological) mutations

Answer 11

Alter normal/wild-type visible phenotype

Question 12

Nutritional (biochemical) mutations

Answer 12

Cause loss in ability to synthesize amino acid or vitamin

Question 13

Gain-of-function mutations

Answer 13

Result in a gene product with enhanced/new function

Question 14

Biochemical mutations

Answer 14

Can have effect on well-being and survival of affected individual

Question 15

Behavioral mutations

Answer 15

Affect behavior patterns of organisms. For example, the mating behavior of the fruit fly may be impaired if it cannot beat its wings.

Question 16

Regulatory mutations

Answer 16

Affect regulation of gene expression

Question 17

Recessive autosomal mutation

Answer 17

Occurs in somatic cell of diploid organism–Is unlikely to result in detectable phenotype

Question 18

X-linked recessive mutations

Answer 18

• Arise in gametes of homogametic female

- May be expressed in hemizygous male offspring

Question 19

Lethal mutations

Answer 19

• Interrupt essential process and result in death

- Various inherited biochemical disorders

Question 20

Conditional mutations

Answer 20

• Dependent on organism’s environment
  Temperature-sensitive mutation
• Gene product functions at one temperature but not another

Question 21

Neutral mutation

Answer 21

• Occurs in protein-coding region or in any part of genome
• Vast majority of mutations likely to occur in large portions of genome that do not contain genes
• Do not affect gene products or gene expression
• The effect on genetic fitness of organism is neither beneficial nor detrimental.
• Neutral effect on genetic fitness of organism

Question 22

Classification Based on Location of Mutation

Answer 22

1. Somatic mutations occur in any cell except germ cells; they are not heritable.
2. Germ-line mutations occur in gametes; they are inherited.
3. Autosomal mutations occur within genes located on autosomes.
4. X-linked and Y-linked mutations occur within genes located on X and Y chromosome, respectively.

Question 23

Spontaneous and Induced Mutations

Answer 23

Spontaneous mutations
– Happen naturally and randomly
– Usually linked to normal biological or chemical processes in organism
— alter structure of nitrogenous bases
– Occur during enzymatic process of DNA replication

Question 24

DNA Replication Errors and Slippage

Answer 24

Mutations arise from replication
– Replication is imperfect.
– DNA polymerase occasionally inserts incorrect nucleotides.
– Misincorporated nucleotides persist after proofreading.
– Errors due to mispairing predominantly lead to point mutations.

Question 25

Replication slippage

Answer 25

• If loop occurs in template strand during replication, DNA polymerase misses looped out nucleotides, and small insertions and deletions occur.
• Replication slippage is more common in repeat sequences
  1. Hot spots for DNA mutation
  2. Contributes to hereditary diseases
  (Fragile-X, Huntington disease)

Question 26

Tautomeric Shifts

Answer 26

1. Tautomers
   - Purines and pyrimidines exist in tautomeric forms
   (alternate chemical forms)
   - Increase chance of mispairing during DNA replication
2. Tautomeric shifts
   - Can change the bonding structure, allowing noncomplementary base pairing
   - May lead to permanent base-pair changes and mutations (Figure14-2 and Figure14-3)

Question 27

Depurination and Deamination

Answer 27

1. DNA base damage
   - Depurination and deamination
   - Common causes of spontaneous mutations
   - Lead to new base pairing and mutations

Question 28

Depurination and Deamination

Answer 28

1. Depurination
   – Loss of nitrogenous bases (usually purine—guanine or adenine), leads to apurinic site (without purine)
2. Deamination
   - Amino group in cytosine or adenine converted to uracil
   (adenine converted to hypoxanthine)
   - Result: change in base pairing of original bases
   A=T converted to G=C
   Figure14-4

Question 29

Mutagens

Answer 29

Mutagens: Natural or artificial agents that induce mutations
–All cells are exposed to a plethora of mutagens.
–Fungal toxins
–Cosmic rays
–Ultraviolet light
–Industrial pollutants
–Medical X rays
–Chemicals in tobacco smoke

Question 30

Base analogs (mutagenic chemicals)

Answer 30

–Can substitute for purines or pyrimidines during nucleic acid biosynthesis
–Increase tautomeric shifts
–Increase sensitivity to UV light (mutagenic)
–Example: 5-Bromouracil behaves as thymine analog. (Figure 14-5)

Question 31

Alkylating, Intercalating, and Adduct-Forming Agents

Answer 31

Alkylating agents
–Donate alkyl group (CH3 or CH3CH3) to amino or keto groups in nucleotides
–Alter base-pairing affinity
–Transition mutations result
–Example: mustard gas

Question 32

UV light

Answer 32

1. UVlight
   – Electromagnetic spectrum (Figure 14-7)
   – Purines and pyrimidines absorb UV at 260 nm.
2. UV radiation creates pyrimidine dimers.
   – Two identical pyrimidines that distort DNA conformation – Errors can be introduced during DNA replication. (Figure14-8)

Question 33

Ionizing radiation

Answer 33

– Energy of radiation varies intensely with wavelength.
– Mutagenic: X rays, gamma rays, cosmic rays
– Penetrates deeply into tissues
– Causes ionization of molecules

Question 34

Free radicals

Answer 34

–Stable molecules transformed into free radicals (chemical species containing 1 or 1+ unpaired electrons)
–Free radicals directly/indirectly affect DNA.
- Alter purines and pyrimidines
- Break phosphodiester bonds
- Produce deletions, translocations, and fragmentation

Question 35

Oxidative damage to DNA

Answer 35

• Due to by-products of normal cellular processes
• Exposure to high-energy radiation
• Superoxides (O2–)
• Hydroxyl radicals (OH)
• Hydrogen peroxide (H2O2)

Question 36

DNA Repair

Answer 36

Repair systems counteract spontaneous and induced DNA damage.

• DNA repair system: maintains integrity of genetic material
• Repair systems counteract genetic damage that would result in genetic diseases and cancer.

Question 37

Proofreading and Mismatch Repair

Answer 37

• DNA polymerase “proofreads,” removes, and replaces incorrectly inserted nucleotides.
• Mismatch repair (if proofreading fails) becomes activated.
• Mismatches are detected, cut, and removed (endonuclease and exonuclease). Correct nucleotide is inserted by DNA polymerase.

Question 38

Defective Mismatch Repair

Answer 38

Strong link between defective mismatch repair, and cancer has been documented.

• Hereditary nonpolyposis colon
• Leukemia
• Lymphoma
• Tumors of ovary, prostate, and endometrium

Question 39

Photoreactivation repair (PRE)

Answer 39

– Cleaves bonds between thymine dimers (T-T), reversing effect of UV radiation on DNA (Figure 14-10)
– Enzyme must absorb photon of light to cleave dimer.

Humans and other organisms lack photoreactivation repair.

Question 40

Base and nucleotide excision repair (BER & NER)

Answer 40

• Light-independent DNA repair mechanisms exist in all prokaryotes and eukaryotes and involve excision repair.
• Exonuclease recognizes and cuts distortion/error.
• DNA polymerase inserts complementary nucleotides in missing gap.
• DNA ligase seals final “nick.”

Question 41

Excision repair (2 types)

Answer 41

Two types of excision repair

1. Base excision repair (BER)
   - Corrects DNA containing a damaged DNA base (f 14-11)
   - DNA glycosylase recognizes altered base.
2. Nucleotide excision repair (NER)
   - Repairs bulky lesions that alter/distort double helix (Figure14-12)

Question 42

Nucleotide Excision Repair and Xeroderma Pigmentosum

Answer 42

Xeroderma pigmentosum (XP)
– Rare genetic disorder due to defects in NER pathways 
– Affected individuals exhibit severe skin abnormalities, skin cancers, and developmental and neurological defects.
– Individuals have a 2000-fold higher rate of cancer. (Figure 14-13)

Question 43

The Ames Test Is Used to Assess the Mutagenicity of Compounds

Answer 43

Ames test
– Uses different strains of Salmonella typhimurium that are able to reveal presence of specific mutations
– Assay measures frequency of reverse mutations in mutant gene.
– Used extensively during development of industrial and pharmaceutical chemical compound
– Many known carcinogens shown by Ames test to be strong mutagens
– More than 60 compounds found in cigarette smoke test positive and cause cancer in animals.

Question 44

Transposable Elements Move within the Genome and May Create Mutations

Answer 44

Transposable elements (transposons)
–“Jumping genes” can move w/in and b/w chromosomes
– Insert themselves into various locations w/in genome
– Found in all organisms; precise function still unknown

Question 45

Transposable Elements in Humans

Answer 45

Human transposable elements
– Half of human genome is composed of transposable elements.
– LINEs and SINEs: long interspersed elements and short interspersed elements
0.2% of detectable human mutations may be due to transposable element insertions.–Transposons may contribute to variability that underlies evolution.

Question 46

Transposons, Mutation, and Evolution

Answer 46

Transposons can have a wide range of effects on genes.
– Insertions can lead to translation disruptions.
–Transposon promoters and enhancers can have effects on nearby genes.
–Transposons can cause aberrant splicing and early transcription translation.
– Recombination between transposons can lead to chromosomal rearrangements, resulting in phenotypic changes or disease.

Question 47

Polygenic and Monogenic Diseases

Answer 47

Polygenic
–Most human genetic diseases are polygenic, caused by variations in several genes.
Monogenic diseases
–Single base-pair change in one of approximately 20,000 human genes may lead to serious inherited disorders. (Table 14.1)