12.1-12.6

Question 1

mutation frequency

Answer 1

can be measured in bacteria and other haploid microorganisms by the number of times mutation alters a particular gene

in sexually reproducing diploids, it is the number of mutational events in a given gene over a given unit of time; and while recessive mutations can be identified, it is more common to identify dominant mutations as they are easier to detect. per replication cycle

Question 2

mutation hotspots

Answer 2

genes or areas of the genome where mutations occur much more than the average

Question 3

point mutation

Answer 3

a mutation that occurs in a particular location on a genome

Question 4

base-pair substitution mutation

Answer 4

the replacement of one nucleotide base pair by another
two types:
transition mutations
transversion mutations

Question 5

transition mutation

Answer 5

base pair substitution in which one purine (A or G) replaces the other or one pyramidine replaces the other (C or T)

Question 6

transversion mutation

Answer 6

a purine is replaced by a pyramidine or vice versa

Question 7

silent mutations

Answer 7

base-pair substitutions producing a protein with the same amino acid sequence as the wild-type protein

Question 8

missense mutation

Answer 8

a base pair substitution that results in one amino acid change to the protein

Question 9

nonsense mutation

Answer 9

a base-pair substitution that creates a stop codon in place of a codon specifying an amino acid

Question 10

frameshift mutation

Answer 10

insertion or deletion of one or more base pairs in a coding sequence of a gene alters every codon in the gene.

Question 11

regulatory mutations

Answer 11

point mutations that have the effect of reducing or increasing the amount of wild-type gene transcript and the amount of wild-type polypeptide

Question 12

promoter mutations

Answer 12

mutations that alter the promoter consensus sequence nucleotides and interfere with efficient transcription initiation.

Question 13

splicing mutations

Answer 13

mutations of consensus sequences marking the 5’ splice site which can result in splicing errors

Question 14

cryptic splice sites

Answer 14

base pair substitution mutations that produce new splice sites that replace or compete with authentic splice sites during pre-mRNA processing

Question 15

forward mutation

Answer 15

converts a wild-type allele to a mutant allele

Question 16

reversion mutation

Answer 16

convert a mutation to a wild type or near wild type

Question 17

true reversion

Answer 17

the wild type DNA sequence is restored to encode its original message by a second mutation at the same site or within the same codon

Question 18

intragenic reversion

Answer 18

reversion that occurs by a second mutation elsewhere in the gene

Question 19

second site reversion

Answer 19

produced by a mutation in a different gene

the example in the book is of a mutation of one gene stops expression of gene A

the second site reversion is a totally other gene mutation promotes expression of gene A causing a reversion

Question 20

spontaneus mutation

Answer 20

naturally occurring mutations arise in cells without being induced by exposure of DNA to a physical, chemical, or biological agent capable of creating DNA damage.

arise primarily through errors during DNA replication and through spontaneous changes in the chemical structure of nucleotide bases

Question 21

DNA replication errors

Answer 21

rare due to high fidelity due to proof reading

exception is observed in genomic regions containing repetitive sequences

change the number of base-pairs in repeating sequences and they are another source of hotspots of mutation.

Question 22

strand slippage

Answer 22

DNA replication error mutations that alter the number of DNA repeats

Mechanism:
DNApolymerase of the replisome temporarily dissociates from the template strand as it moves across region of repeating DNA sequence. During dissociation, a portion of newly replicated DNA forms a temporary double-stranded hairpin structure induced by the complementary base pairing of nucleotides in the loop. Reassociation of DNA polymerase and resumption of replication leads to re-replication of a portion of the repeat region, increasing the length of the repeat region in the daughter strand. Repeating DNA sequences are often hotspots of mutation due to strand slippage.

Question 23

trinucleotide repeat disorders

Answer 23

diseases where the wild type alleles of the genes in question normally contain a variable number of DNA trinucleotide repeats. On rare occasiions, these genes undergo mutation through strand slippage events that cause the number of trinucleotide repeats to increase. For each of these examples, expansion of the number of trinucleotide repeats beyond the wild-type range results in a hereditary disorder by blocking the production of wild-type mRNA and reducing or eliminating the production of wild-type protein.

Question 24

tautomeric shift

Answer 24

the most common type of DNA replication error

a nucleotide randomly tautomerizes which makes it bind with G instead of A or C instead of T or vice versa.

tautomers are unstable so they eventually shift back, but when replication happens then, one strand has the normal base pair and the other has the opposite base pair, causing a base-pair substitution

Question 25

Depurination

Answer 25

most common kind of spontaneous mutation the loss of one of the purines, adenine or guanine, from the nucleotide by breakage of the covalent bond at the 1' carbon of deoxyribose that links the sugar to the nucleotide base. nearly all lost purines are replaced before the next DNA replication cycle, but a few are not

Question 26

apurinic site

Answer 26

an un-repaired lesion of purine from de purination. During replication, the apurinic site does not contain a template basem and DNA polymerase usually compensates by placing an adenine (but sometimes guanine) opposite of the site. During the next DNA rep cycle, the strand that has the apurinic site has yet another adenine placed as its complement and the other strand proceeds to be given a Thymine for the previously placed adenine. causing a base pair substitution if the lost purine was Guanine

Question 27

Deamination

Answer 27

the loss of an amino group from a nucleotide base. It is a second form of spontaneous mutation. usually cytosine, which then leads to replacement with oxygen, forming a Uracil. DNA repair mechanisms recognize the Uracil and replace it with a cytosine. if the cytosine has been methylated, it creates a thymine and generates a mismatch. if the mismatch is corrected before the next rep cycle The repair either restores the wild type G-C base pair or the repair generates an A T base pair causing a base pair substitution CpG nucleotides are frequent targets for methylation in promoters where methylation helps regulate transcription, thus making them succeptible to the above mutation. Thus, CpG nucleotides are hotspots for mutation.

Question 28

induced mutations

Answer 28

mutations produced by interactions between DNA and aphysical, chmical, or biological agent that generates damage resulting in mutation.

Question 29

mutagen

Answer 29

an agent that induces mutations

Question 30

how would you classify chemical compounds by their mode of action on DNA

Answer 30

1) nucleotide base analogs 2) deaminating agents 3) alkylating agents 4) oxidizing agents 5) hydroxylating agents 6) intercalating agents

Question 31

base analog

Answer 31

a chemical compound that has a structure similar to one of the DNA nucleotides and therefore can work its way into DNA, where it pairs with a nucleotide. DNA cannot distinguish them from the actual DNA nucleotides thus, base analogs are incorporated into DNA strands during replication

Question 32

bulky adducts

Answer 32

added by alkylating agents bulky side groups such as methyl and ethyl groups added to nucleotide bases

Question 33

intercalating agents

Answer 33

small molecules that squeeze their way between DNA base pairs.

Question 34

photoproduct.

Answer 34

altered DNA from radiation. usually UV pyrimidine dimer thymine dimer 6-4 photoproduct

Question 35

pyrimidine dimer

Answer 35

photoproduct produced by the formation of one or two additional covalent bonds between adjacent pyrimidine dinucleotides in a strand of DNA.

Question 36

6-4 photoproduct

Answer 36

joins adjacent thymines by formation of a bond between the 6 carbon of one thymine and the 4 carbon of the other thymine

Question 37

translesion DNA synthesis

Answer 37

carried out by specialized bypass DNA polymerases that can replicate across the gaps in DNA usually caused by DNA polymerase skipping over the segment of the strand containing pyramidine dimers. more prone to replication error because they lack proofreading ability due to the fact that no proof reading allows them to continue replication over pyramidine dimers.