Anatomy and Function of a Gene: Dissection Through Mutation I

  1. Genes with one common allele are _________, while genes with several common alleles in natural population are ________.
    • monomorphic 
    • polymorphic
  2. Define wild type allele in terms of monomorphic genes
    The allele that is found on the large majority of chromosomes in the population under consideration is wild type
  3. Define wild type allele in terms of polymorphic genes
    Less straightforward, some geneticists consider all alleles with a frequency of greater than 1% to be wild type, while others describe the many alleles present at appreciable frequencies in the population as common variants and reserve "wild type allele: for use only in connection with monomorphic genes
  4. A mutation that changes a ____ _____ allele of a gene (regardless of definition) to a _______ allele is called a forward mutation. The resulting novel mutant allele can be either _______ or _______ to the original ______ ______ allele
    • wild-type
    • different
    • recessive or dominant
    • wild type allele
  5. How do geneticists diagram forward mutations?
    A→ a; when the mutation is recessive to the wild type

    b→  B; when the mutation is dominant to wild type
  6. Mutations can also cause a novel mutant allele to revert back to the _____ ______ in a process known as _______ mutation or ________
    • wild type 
    • reverse mutation or reversion
  7. How do geneticists diagram reverse mutations?
    a → A+ or B → b+
  8. Mendel originally defined genes by the visible phenotypic effects (yellow or green, round or wrinkled) of their _______ _______. In fact, the only way he knew that genes existed at all was because alternative alleles for seven particular pea genes had arisen through ________ mutations
    • alternative alleles
    • forward
  9. Mutations can occur in ______ cells or in ______ cells. The mutations in Mendel's pea plants were heritable because they occurred in the _____ cells of the plants and were thus transmitted through ______.
    • somatic cells
    • germ-line cells
    • germ-line cells
    • gametes
  10. Close to a century later, knowledge of DNA structure clarified that such mutations are _______ changes in DNA base sequence. DNA thus carries the potential for genetic changes in the same place it carries genetic information aka:
    • heritable
    • aka the sequence of its bases
  11. When does a substitution occur?
    What is the result in the daughter double helix?
    Image Upload 1
    • occurs when a base at a certain position in one strand of the DNA molecule is replaced by one of the other three bases
    • after DNA replication, a new base pair will appear in the daughter double helix
  12. Substitutions can be subdivided into ________ and ________
    transitions and transversions
  13. transitions
    • transitions: in which one purine (A  or G) replaces the other purine, or one prymidine (C or T) replaces the other
    • transverions: in which a purine changes to a pyrimidine, or vice versa
  14. deletion
    • deletion: occurs when a block of one or more nucleotide pairs is lost from a DNA molecule
    • insertion: the addition of one or more nucleotide pairs
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  15. Deletions and insertions can be as small as a _______ base pair or as large as _______ (millions of base pairs).
    • single
    • megabases
  16. Large deletions and insertions are only some of the complex mutations that can reorganize genomes by changing either (3):
    • the order of genes along a chromosome
    • the number of genes in the genome
    • the number of chromosomes in an organism
  17. A _____ fraction of the mutations in a genome actually alter the nucleotide sequences of genes in a way that affects gene _______
    • small 
    • function
  18. By changing one allele to another, these (function altering) mutations modify the _______ or _______ of a gene's protein product, and the modification in protein _______ or _______ influences _________.
    • structure or amount
    • structure or amount
    • phenotype
  19. All other mutations either alter genes in ways that do not affect their ______ or change the _____ between genes
    • function 
    • DNA
  20. Mutations that modify gene function happen so _______ that geneticists must examine a very large number of individuals from a formerly ________ population to detect the new ________that reflect these mutations
    • infrequently
    • homogenous 
    • phenotypes
  21. Rates of spontaneous mutations (2-story)
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    • In one ongoing study, investigators have monitored the coat colors of millions of specially bred mice and discovered that on average, a given gene mutates to a recessive allele in roughly 11 out of every 1 million gametes 
    • Studies of several other organisms have yielded similar results: an average spontaneous rate of 2-12 * 106 mutations per gene per gamete
  22. Mutation rates in euks (4) compared to that of proks (3)

    • Higher per generation (many cell divisions per generation)
    • 2-12 x 10-6 mutations per gene per gamete
    • Diploid cells allow for tolerance of mutations
    • *Average human gamete contains 30 mutations


    • Low per generation (single celled)
    • 10-8 to 10-7 per gene per division
    • Single chromosome is more susceptible to disfunction
  23. Detecting revertants (5-story)
    Hint: Gene function is easy to disrupt but hard to restore
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    pg 209
  24. It actually makes sense that sperm carry more mutations than oocytes. (explain)
    There are more rounds of cell divisions are needed to produce human sperm than human eggs, so there have been more opportunities for mutations to occur
  25. Human females are born with essentially all of the _____ ______ they will ever produce. It has been estimated that the germ-line cells of a female zygote need to undergo only ____ rounds of mitotic cell divisions to produce all of these oocytes. Male germ-line, on the other hand, undergo mitosis ______ throughout life
    • primary oocytes 
    • 24
    • continually
  26. Why is it difficult to study the events that produce mutations and how do researchers overcome such difficulty
    • Because spontaneous mutations affecting a gene occur so infrequently 
    • To overcome, researchers turned to bacteria as the experimental organisms of choice. 
    • *It is easy to grow many millions of individuals and then search rapidly through enormous populations to find the few that carry a novel mutation
  27. In one study, investigators spread wild-type bacteria on the surface of ______ containing sufficient nutrients for growth as well as a large amount of a bacteria-killing substance, such as an _______ or ________.
    • agar
    • antibiotic or bacteriophage
  28. Although _____ of the bacterial cells died, a few showed _________ to the bactericidal substance and continued to ______ and ______. The descendants of a single resistant bacterium, produced by many rounds of ______ ______, formed a mound of genetically _______ cells called a colony
    • most
    • resistance
    • grow and divide
    • binary fission
    • identical
  29. In 1934, Salvador Luria and Max Delbrück devised an experiment to examine the origin of _______ _______
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    bacterial resistance
  30. What was Salvador Luria and Max Delbrück's reasoning with regards to the origin of the mutations that were causing the resistance?
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    • If bacteriophage-resistant colonies arise in direct response to infection by bacteriophages, separate suspensions of bacteria containing equal numbers of cells will generate similar, small numbers of resistant colonies when spread in separate petri plates on nutrient agar suffused with phages
    • By contrast, if resistance arises from mutations that occur spontaneously even when the phages are not present, then different liquid cultures, when spread on separate petri plates, will generate very different numbers of resistant colonies
  31. The mutation conferring resistance can, in theory, arise at any _______ during the growth of the culture. If it happens early, the cell in which it occurs will produce _____ _____ progeny prior to petri plating; if it happens later, there will be far ______ _____  progeny when the time for plating arrives
    • time
    • many mutant 
    • fewer mutant
  32. After plating, these numerical differences will show up as _________ in the numbers of resistant colonies growing in the different petri plates
  33. What were the results of the fluctuation test? (3-story)
    pg 210-211
  34. Replica plating
    a process whereby colonies on a master plate are picked up on velvet and then transferred to media in other petri plates to test for phenotype
  35. Researchers used another technique known as _____ _____ to demonstrate even more directly that the mutations conferring bacterial resistance occur _______ the cells encounter the bactericide that selects for their resitance
    • replica plating 
    • before
  36. These key experiments showed that bacterial resistance to phages and other batericides is the result of ________, and these ________ do not arise in particular genes as a directed response to _________ change
    • mutations 
    • mutations
    • environmental
  37. Instead, mutations (in resistant colonies) occur ________ as a result of _______ processes that can happen at _____ time and hit the genome at _____ place
    • spontaneously 
    • random
    • any
    • any
  38. Once such random changes occur however, they usually remain ______. If the resistant mutants of the Luria and Delbrück experiment, for example, were grown for many generations in medium that did not contain bacteriophages, they would nevertheless remain _______ to this bactericidal virus
    • stable
    • resistant
  39. Replica plating verifies that bacterial resistance is the result of preexsiting mutations
    Part a (3-Story) and Part b (2-story)
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    pg 212
  40. The creation of a heritable mutation is the outcome of several competing process: ______, ______, and _______
    • mutation, repair and replication
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  41. First, of course, a _______ event must occur to alter the DNA. Two different kinds of events initiate DNA changes. Name them
    • random
    • Either DNA can be damaged by chemical reactions or irradiation
    • Alternatively, mistakes can occur when DNA is copied during replication
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  42. Just after being made, DNA changes are not yet actual mutations but only potential mutations. (why?)
    because most of them are quickly repaired by a variety of enzymatic systems within cells
  43. These DNA repair machines are engaged in a continual race with _____ ________. If repair of damaged DNA or misincorporated nucleotides occurs ______ the next round of ____ _______, then the sequence is corrected and no mutation will result
    • DNA replication
    • before
    • DNA replication
  44. However, if the repair enzymes do not correct the problem _______ the next round of ____ _______, the mutation becomes _______ established in both strands of the double helix and a _______ mutation is the outcome
    • before
    • DNA replication
    • permanently 
    • heritable
  45. Chemical and physical assaults on DNA are quite ________. Geneticists estimate, for example, that the ________ of a purine base, A or G, from the deoxyribose-phosphate backbone occurs _____ times an hour in every human cell
    • frequent
    • hydrolysis
    • 1000
  46. Depurination
    Image Upload 11
    DNA alteration in which the hydrolysis of a purine base, either A or G, from the deoxyribose-phosphate backbone occurs
  47. Why does the DNA replication process introduce a random base opposite the apurinic site? What is the result?
    • Because the resulting apurinic site cannot specify a complementary base
    • This causes a mutation in the newly synthesized complementary strand three-quarters of the time
  48. Deamination
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    yet another naturally occurring modification of DNAs info in which an amino group (-NH2) is removed
  49. Deaminiation can change cytosine (C) to _______, the nitrogenous base found in RNA but not in DNA
    uracil (U)
  50. Why is it that deamination followed by replication may alter a C-G base pair to a T-A pair in future generation of DNA molecules? What kind of mutation is this?
    • Because U pairs with A rather G
    • transition mutation
  51. Other assaults include naturally occurring radiation such as ______ ______ and _______ which break the sugar phosphate backbone
    • cosmic rays and X-rays
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  52. Ultraviolet light is another possible source of assault which causes adjacent _______ residues to become chemically linked into _______-______ _______
    • thymine
    • thymine-thymine dimers
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  53. In the image, _______ damage is done to _____ of the four bases. If not repaired before DNA replication, all of these changes alter the info of the DNA molecule ________
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    • oxidative
    • one
    • permanently
  54. If the cellular machinery for some reason incorporates an incorrect base during replication, for instance, a C opposite an A instead of the expected T, what happens during the next replication cycle?
    One of the daughter DNAs will have the normal A-T base pair while the other will have a mutant G-C
  55. Careful measurements of the fidelity of replication in vivo, in both bacteria and human cells, show that such errors are exceedingly _____
    rare (less than 1 in 109 base pairs)
  56. The replication machinery ________ errors through successive stages of correction. In the test tube, DNA polymerases replicate DNA with an error rate of about one mistake in every _____ bases copied
    • minimizes
    • 106
  57. This rate is about ______ fold worse than that achieved by the cell. Even so, it is impressively low and is only attained because polymerase molecules provide, along with their ________ function, a _______/_______ function in the form of a _______ that is activated whenever the polymerase makes a ________
    • 1000
    • polymerization
    • proofreading/editing
    • nuclease
    • mistake
  58. This nuclease portion of the polymerase molecule called the _______ ___________,recognizes a mispaired bases and _______ it,  allowing the polymerase to copy the nucleotide ________ on the next try
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    • 3'-to-5' exonuclease
    • excises 
    • correctly
  59. Without its nuclease portion, DNA polymerase would have an error rate of one mistake in every ____ bases copied, so its editing function improves the fidelity of replication _____ fold
    • 104
    • 100
  60. DNA polymerase in vivo is part of a replication system including many other proteins that collectively improve on the error rate another 10-fold, bringing it to within about 100-fold of the fidelity attained by the cell. The 100-fold higher accuracy of the cell depends on a back up system called ______ ______ ________ repair. What does it do?
    • methyl-directed mismatch repair
    • It notices and corrects residual errors in the newly replicated DNA
  61. Tautomerization
    interconversion of bases between two similar forms, or tautomers
  62. Tautomerization is a reason _____ _______ can make mistakes. Each of the four bases has two _______, similar chemical forms that _________ continually
    • DNA polymerase
    • tautomers
    • interconvert
  63. The _______ between the tautomers is such that each base is almost ______ in the form in  which A pairs with T and G pairs with C.
    • equilibrium
    • always
  64. If, by chance, a base in the template strand is in its rare tautomeric form when DNA polymers arrives, what happens?
    • The wrong base will be incorporated into the newly synthesized chain because the rare tautomers pair differently than do the normal forms
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  65. If the misincorporated nucleotide is not corrected by mismatch repair before the next round of replication, a ______ mutation occurs
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    point mutation
  66. In 1992, molecular geneticists discovered a completely unexpected type of mutation in humans: the excessive amplication of a _____ base triplet normally repeated on a few to 50 times in succession. If, for example, a normal allele of a gene carries five consecutive repetitions of the base triplet ________, an abnormal allele could carry _____ repeats in a row
    • CGG
    • CGG
    • 200
  67. Repeats of several other trinucleotides (CAG, CTG, GCC, and GAA) can also be ________, such that the number of repeats often ______ or _______ in different cells of a single individual
    • unstable 
    • increases or decreases
  68. Instability can also occur during gamete production, resulting in changes in ______ _____ from one generation to the next
    repeat number
  69. Unstable trinucleotide repeats have now been found within about 20 different human genes, all associated with ___________ diseases. In all cases, an expansion of the repeats beyond a _____ ______ results in a disease-causing allele. State two examples
    • neurodegenrative diseases
    • certain number
    • Fragile X syndrome (most common form of mental retardation in boys) and Huntington disease (a neurological disorder)
  70. A general feature of both groups of trinucleotide repeat diseases is that the _____ _______ at a particular location, the higher the probability that _______ and _______ will occur
    • more repeats
    • expansion and contraction
  71. Pre-mutation alleles
    a normally functioning allele of an unstable trinucleotide repeat gene with a repeat region expanded to the point where further expansion to a disease allele occurs at high frequency
  72. Why do some alleles with intermediate numbers of trinucleotide repeats behave as so called pre-mutation alleles
    • Because larger repeat number mean more instability (a)
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  73. For example, in fragile X syndrome, individuals with pre-mutation alleles have ______ phenotypes, but the expanded repeat number  means that such __________ alleles are highly likely to expand or contract during ________
    • normal 
    • pre-mutation
    • replication
  74. Carriers of pre-mutation alleles thus have a _____ probability of giving new diseases (with ________ numbers of repeats) to their children
    • high 
    • expanded
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  75. The approximately 20 known neurogenerative diseases caused by genes with unstable trinucleotide (triplet) repeats fall into two categories (name them)
    polyQ diseases and non-polyQ diseases (where Q is the symbol for the amino acid glutamine)
  76. In polyQ disease genes, the repeated triplet is always _____, while in non-polyQ disease genes, __________ repeat may be either CGG, CTG, GCC or GAA.
    • CAG
    • trinucleotide repeat
  77. The two types of triplet repeat diseases are distinguished by the effect of the repeat sequence on gene function. How does this work in both disease types?
    • In polyQ diseases, a disease allele with too many tirplet repeats encodes an abnormal protein
    • Non-polyQ disease alleles encodes either no protein or decreased protein amounts
  78. Huntington disease is a ______ disease; and fragile X syndrome, is a ______ disease
    • polyQ
    • non-polyQ
  79. Each CAG specifies that the amino acid _______ (Q) should be added to the HD protein, so the normal protein 6-28 Q amino acids in a row in its so-called ______ region.
    • glutamine
    • polyQ
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  80. An HD allele with ___ or more repeats encodes a mutant HD protein with an _______ polyQ region that is ______ to nerve cells. Proteins encoded by pre-mutation alleles function _______, but have an ______ repeat number
    • 36 
    • expnaded
    • toxic
    • normally
    • unstable
  81. Why are polyQ disease alleles like ___ called gain of function mutants
    • HD
    • because they encode proteins whose functions are qualitatively different from those of the corresponding wild-type protein
  82. Typical for many gain of function mutants, polyQ disease alleles show ________ inheritance (why?)
    • dominant 
    • because the mutant polyQ proteins are toxic even in the presence of the normal proteins
  83. The disease is caused by expansion of CGG repeat region in an ______ gene called FMR-1 (Fragile X mental retardation-1)
  84. The CGGs of FMR-1 are located in a region of the gene outside of the ORF called the _______
    • 5' UTR
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  85. Normal FMR-1+ genes have 6-55 CGG repeats; expansion of the repeat number to ______ CGGs or more results in an FMR-1 disease allele that is ______ to produce the FMR-1 protein
    • 200
    • unable
  86. Without FMR-1 protein, nerve cells cannot properly form connections called _______. A common feature to all non-polyQ diseases is that the triplets are located in a part of the gene ______ of the ORF. The expanded repeats in non-polyQ disease genes generally prevent ______ production, and so non-polyQ disease genes are ______ of function alleles
    • synapses
    • outside
    • protein 
    • loss of function
Card Set
Anatomy and Function of a Gene: Dissection Through Mutation I
Ch 7