Genetics: From Genes to Genomes
6th Edition
ISBN: 9781259700903
Author: Leland Hartwell Dr., Michael L. Goldberg Professor Dr., Janice Fischer, Leroy Hood Dr.
Publisher: McGraw-Hill Education
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Chapter 7, Problem 23P
In human DNA, 70% of cytosine residues that are followed by guanine (so-called CpG dinucleotides, where p indicates the phosphate in the phosphodiester bond between these two
| a. | Methylated CpG dinucleotides are hotspots for point mutations in human DNA. Can you propose a hypothesis that explains why? | Making the simplifying assumptions that human DNA has an equal number of C–G and A–T base pairs, and that the human DNA sequence is random, how frequently in the human genome would you expect to find the base sequence CpG? |
| c. | It turns out that, even after taking into account the actual GC content of human DNA (˜42%), the frequency of CpG in human DNA is much lower than predicted by the calculation in part (b). Explain why this might be the case. | |
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In human DNA, 70% of cytosine residues that are followed by guanine (so-called CpG dinucleotides, where p indicates the phosphate in the phosphodiester bond between these two nucleotides) are methylated to form 5-methylcytosine. As shown in the following figure, if 5-methylcytosine should undergo spontaneous deamination, it becomes thymine. Methylated CpG dinucleotides are hotspots for point mutations in human DNA. Can you propose a hypothesis that explains why?
In human DNA, 70% of cytosine residues that are followed by guanine (so-called CpG dinucleotides,
where p indicates the phosphate in the phosphodiester bond between these two nucleotides) are
methylated to form 5-methylcytosine. As shown in the following figure, if 5-methylcytosine should
undergo spontaneous deamination, it becomes thymine.
2.
NH,
Deamination
5-methylcytosine
Thymine
Methylated CpG dinucleotides are hotspots for point mutations in human DNA. Can you propose a
hypothesis that explains why?
You want to study the effect of lysine methylation on gene regulation. The lysine amino
acid sidechain is -CH2CH2CH2CH2NH2. To begin to study the relevant functional groups,
you take free CH3CH2CH2CH2NH2 in the lab and decide to try to turn it into the product
(P) CH3CH2CH2CH2NHCH3.
7.
a) Suggest a simple reagent to carry out the desired transformation. (In the
subsequent parts of the problem, you may call this reagent R for short).
b) Draw the reaction using the arrow formalism.
c) What solvent and pH do you suggest? Why?
d) Is the reaction first order or second order?
e) Write down a simple rate equation for dP/dt. If you include any constant(s), what
are their units?
f) In addition to the desired product P, name at least one other impurity (containing
both carbon and nitrogen, you may call this compound U for short) that is likely to
occur in substantial amounts.
g) What choice of initial conditions would bias towards production of substantially
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Chapter 7 Solutions
Genetics: From Genes to Genomes
Ch. 7 - The following is a list of mutational changes. For...Ch. 7 - What explanations can account for the following...Ch. 7 - The DNA sequence of one strand of a gene from...Ch. 7 - Among mammals, measurements of the rate of...Ch. 7 - Over a period of several years, a large hospital...Ch. 7 - Suppose you wanted to study genes controlling the...Ch. 7 - In a genetics lab, Kim and Maria infected a sample...Ch. 7 - The results of the fluctuation test Fig. 7.5 were...Ch. 7 - The following pedigree shows the inheritance of a...Ch. 7 - Autism is a neurological disorder thought to be...
Ch. 7 - Like the yellow Labrador retrievers featured in...Ch. 7 - Remember that Balancer chromosomes prevent the...Ch. 7 - Figure 7.14 shows examples of base substitutions...Ch. 7 - Figure 7.14a shows the mutagen 5-bromouracil 5-BU,...Ch. 7 - So-called two-way mutagens can induce both a...Ch. 7 - In 1967, J. B. Jenkins treated wild-type male...Ch. 7 - When a particular mutagen identified by the Ames...Ch. 7 - Prob. 18PCh. 7 - The Ames test uses the reversion rate His- to His...Ch. 7 - The mutant FMR-1 allele that causes fragile X...Ch. 7 - The physicist Stephen Hawking, famous for his...Ch. 7 - Aflatoxin B1 is a highly mutagenic and...Ch. 7 - In human DNA, 70 of cytosine residues that are...Ch. 7 - Bromodeoxyuridine BrdU is a synthetic nucleoside...Ch. 7 - Albinism in animals is caused by recessive...Ch. 7 - a. In Figure 7.22b, what can you say about the...Ch. 7 - Imagine that you caught a female albino mouse in...Ch. 7 - Plant breeders studying genes influencing leaf...Ch. 7 - In humans, albinism is normally inherited in an...Ch. 7 - a. Seymour Benzers fine structure analysis of the...Ch. 7 - a. You have a test tube containing 5 ml of a...Ch. 7 - Prob. 32PCh. 7 - The rosy ry gene of Drosophila encodes an enzyme...Ch. 7 - Nine rII- mutants of bacteriophage T4 were used in...Ch. 7 - In a haploid yeast strain, eight recessive...Ch. 7 - In Problem 24, you learned that Bloom syndrome is...Ch. 7 - The pathway for arginine biosynthesis in...Ch. 7 - In corn snakes, the wild-type color is brown. One...Ch. 7 - In a certain species of flowering plants with a...Ch. 7 - The intermediates A, B, C, D, E, and F all occur...Ch. 7 - In each of the following cross schemes, two...Ch. 7 - Prob. 42PCh. 7 - The following complementing E. coli mutants were...Ch. 7 - In 1952, an article in the British Medical Journal...Ch. 7 - Mutations in an autosomal gene in humans cause a...Ch. 7 - Antibodies were made that recognize six proteins...Ch. 7 - Prob. 47PCh. 7 - Prob. 48PCh. 7 - In addition to the predominant adult hemoglobin,...Ch. 7 - Most mammals, including New World primates such as...Ch. 7 - Humans are normally trichromats; we have three...
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Need a deep-dive on the concept behind this application? Look no further. Learn more about this topic, biology and related others by exploring similar questions and additional content below.Similar questions
- 5-Bromouracil is a compound that is known to induce point mutations in DNA. 1) Out of A/C/G/T as drawn, which nucleobase pairs best with 5-bromouracil? Briefly explain why? ii) The bromine of 5-bromouracil stabilises the alternative tautomeric form of the lactam at position 4. Describe in words the structure of this alternative lactim tautomer of 5-bromouracil. iii) Identify the nucleobase (A/C/G/T) which can best base pair with this alternative tautomer.arrow_forwardOf the four DNA bases, why is guanine most likely to be modified after exposure to polycyclic hydrocarbons such as benzo(a)pyrene, as shown in Figure 23.8? (Hint: Consider the pKa values of the four DNA bases.)arrow_forwardIn E. coli, all newly synthesized DNA appears to be fragmented (an observation that could be interpreted to mean that the leading strand as well as the lagging strand is synthesized discontinuously). However, in E. coli mutants that are defective in uracil–DNA glycosylase, only about half the newly synthesized DNA is fragmented. Explain.arrow_forward
- Write a balanced equation for the hydrolytic deamination of a DNA5-methylcytosine residue.arrow_forwardWrite a balanced equation for the hydrolytic deamination of a DNA-5- methylcytosine residue.arrow_forwardWrite a balanced equation for the hydrolytic deamination of a DNA- 5-methylcytosine residue.arrow_forward
- a) It is known that double stranded DNA is denatured at low pH. pKa values should allow the determination of whether this is due to perturbation of the hydrogen bonding in A-T and/or G-C base pairs. The table gives values for the pKas of different protonated groups in the nucleobases.Nucleobase Position & pKa A N1, 3.5 G N7, 1.6; N1, 9.2 C N3, 4.2 T N3, 9.7a) Draw the A-T and G-C base pairs. - Label the bases with the one-letter code. – - Number the atoms in the rings and label the atom that attaches to the sugar. - Mark the groups that interact in normal…arrow_forwardWhat is the length in AA’s of the LilP protein? Assume fMet is NOT CLEAVED. Enter just the number, nothing else! Write out the sequence of the polypeptide in AA: use the three letter notation, e.g. Met-Ser-Pro- A lilP mutant called lilPXS is isolated that produces a truncated polypeptide of only 6 AA in length. Describe a single basepair DNA change that would lead to this truncated version of the protein. Multiple options are possible (100 words max.)arrow_forwardIn the following sequence, a cytosine was deaminated and is now a uracil (underlined). 5’-GGTAUTAAGC-3’ a. Which repair pathway(s) could restore this uracil to cytosine? b. If the uracil is not removed before a DNA replication fork passes through, what will be the sequences of the two resulting double helices? Provide the sequences of both strands of both helices. Label the old and new strands and underline the mutation(s). c. Could the mismatch repair pathway fix the mutations you’ve indicated in part b? d. If the cell undergoes mitosis, and the replicated DNAs are distributed into the two daughter cells. Will 0, 1, or 2 daughter cells have a mutation in this sequence?arrow_forward
- The base analog 5-bromouracil (5BU), which sterically resembles thymine, more readily undergoes tautomerization from its keto form to its enol form than does thymine. 5BU can be incorporated into newly synthesized DNA when it pairs with adenine on the template strand. However, the enol form of 5BU pairs with guanine rather than adenine. (a) Draw the 5BU · G base pair. (b) What type of mutation results?arrow_forwardEnediynes are natural products with potent antitumor properties because they are able to cleave DNA (page 288). Their cytotoxic properties are due tothe enediyne undergoing a cyclization to form a highly reactive diradical intermediate. The intermediate abstracts hydrogen atoms from the backbone of DNA, which triggers its damage. Draw the structure of the diradical intermediate.arrow_forward5'....TACTGCCCATGCCCAGAGAGAAAGCGCAGACGCGTCTAA actgt... 3' a). (10 points). In the above sequences, the open reading frame is indicated by alternating non-underlined and underlined triplets. Please use the codon table to deduce the amino acid sequence for the region shown in the wildtype protein. Wildtype AA sequence for the region around mutation #1: Wildtype AA sequence for the region around mutation #2: b). (10 points). Please make predictions what molecular change mutation #1 and mutation #2 cause. c). (5 points). Which mutation is more likely to abrogate the protein function? Why?arrow_forward
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