MIT Biology Department 7.012: Introductory Biology-Fall 2004 Instructors: Professor Eric Lander, Professor Robert A Weinberg, Dr. Claudette Gardel 7.012 Practice Quiz 1 Actual Quiz 1(closed book) will be given Monday10/4 at 10: 00 am No Sections on Monday or tuesday 10/4-10/5(No Kidding Quiz Review Session Thursday, 9/30 7:00-9:00pm Tutoring Session Friday, 10/1 4:00-6:00pm
7.012 Practice Quiz 1 Actual Quiz 1 (closed book) will be given Monday10/4 at 10:00 am No Sections on Monday or Tuesday 10/4-10/5 (No Kidding.) Quiz Review Session Thursday, 9/30 7:00 - 9:00 pm Tutoring Session Friday, 10/1 4:00 - 6:00 pm MIT Biology Department 7.012: Introductory Biology - Fall 2004 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel
Question 1 Shown below are the structures of three amino acids NH NH, OH H-C-CH CH H-C-CH OH Phenylalanine Threonine (Phe) ( yr) Using the blanks below, rank these three in order of the hydrophobicity of their side chaIns b)工 ntermediate Leas↑ Hydrophobic d)Explain why(a) is more hydrophobic than(b) e)Explain why(b) is more hydrophobic than(c) Question 2 Shown below is a close up of a substrate(UDP-Glucose) bound to the active site of an enzyme (UTase). The shaded area is the enzyme; the structure of the substrate is shown. CHOH Ser161 NH2 HH CH2 OH H OH OH (Arg 31 Two amino acids of the enzyme are highlighted: Arg 31 and Ser 161
2 Question 1 Shown below are the structures of three amino acids. NH3 C C H O O CH OH CH3 NH3 C CH2 C H O O OH Threonine (Thr) Phenylalanine (Phe) Tyrosine (Tyr) NH3 C CH2 C H O O Using the blanks below, rank these three in order of the hydrophobicity of their side chains. a) Most Hydrophobic b) Intermediate c) Least Hydrophobic d) Explain why (a) is more hydrophobic than (b). e) Explain why (b) is more hydrophobic than (c). Question 2 Shown below is a close up of a substrate (UDP-Glucose) bound to the active site of an enzyme (UTase). The shaded area is the enzyme; the structure of the substrate is shown. N N H OH OH H H O H CH2 O O O P O O O P H CH2OH OH H OH H O H OH H O H NH2 O H Ser161 Arg 31 Two amino acids of the enzyme are highlighted: Arg 31 and Ser 161
Question 2, continued a)Part(I)of the figure below shows the relative positions of Arg 31 and the portion of the substrate with which it interacts; part(Ir)shows the structure of arginine (D) NH H 88 H-C-CH2--CH2-CH2-N The side chain of Arg 31 interacts with the portion of the substrate shown previously What type of interaction()is/are possible between the side chain of Arg 31 and this portion of the substrate?(circle all that apply hydrop orogen IonIc van der Interaction Interaction b)Part(r)of the figure below shows the relative positions of Ser 161 and the portion of the substrate with which it interacts: part(Ir) shows the structure of serine (I Ser161 O+1-O Serine i) The side chain of Ser 161 interacts with the portion of the substrate shown above What type of interaction(s) is/are possible between the side chain of Ser 161 and this portion of the substrate?(circle all that apply hydrophobic Hydrogen IonIc van der waa interaction bond bond interaction i) The side chain of Ser 161 interacts with the region of the substrate shown above Draw the structure of Ser 161 and the relevant portion of the substrate as they would interact with each other. Be sure to indicate (1) the interaction use a dotted line) (2)the places where Ser 161 connects with the backbone of the protein 3
3 Question 2, continued a) Part (I) of the figure below shows the relative positions of Arg 31 and the portion of the substrate with which it interacts; part (II) shows the structure of arginine. (I) (II) Arginine O O O P O O O P O Arg 31 C CH2 CH2 CH2 C H O N H C NH2 NH2 NH The side chain of Arg 31 interacts with the portion of the substrate shown previously. What type of interaction(s) is/are possible between the side chain of Arg 31 and this portion of the substrate? (circle all that apply) hydrophobic Hydrogen ionic van der Waals interaction bond bond interaction b) Part (I) of the figure below shows the relative positions of Ser 161 and the portion of the substrate with which it interacts; part (II) shows the structure of serine. Serine O O O P O O O P O Ser161 (I) C CH2 C H O OH NH i) The side chain of Ser 161 interacts with the portion of the substrate shown above. What type of interaction(s) is/are possible between the side chain of Ser 161 and this portion of the substrate? (circle all that apply) hydrophobic Hydrogen ionic van der Waals interaction bond bond interaction ii) The side chain of Ser 161 interacts with the region of the substrate shown above. Draw the structure of Ser 161 and the relevant portion of the substrate as they would interact with each other. Be sure to indicate: (1) the interaction (use a dotted line) (2) the places where Ser 161 connects with the backbone of the protein
Question 2, continued c)Suppose that you are studying the interactions between the substrate and the enzyme. It is possible to make variant enzymes that differ from the one above by a single amino acid substitution (For example, Asp 78 could be replaced with tryptophan). you could use this technique to investigate the roles of each amino acid shown above i)If you change Arg 31 to a lysine, would you predict that the substrate still binds, or that the substrate now fails to bind to the altered enzyme? Explain. Choose an amino acid substitution for ser 161 ii) Explain the possible outcome of this change Note: There are many possible full-credit answers for (i) and (ii). a table of amino acid structures can be found at the end of this exam Question 3 a)Brief ly define the following Dominant Recessive Phenotype enotype alleles Homozygous Heterozygous Mendel's first Law: Mendel,s second Law Diploid b)A yeast cell has the genotype AaBb, where the a and the b loci are on different chromosomes. Sketch the chromosome arrangement of this cell in meiosis I, when 2n 4 4
4 Question 2, continued c) Suppose that you are studying the interactions between the substrate and the enzyme. It is possible to make variant enzymes that differ from the one above by a single amino acid substitution. (For example, Asp 78 could be replaced with tryptophan). You could use this technique to investigate the roles of each amino acid shown above. i) If you change Arg 31 to a lysine, would you predict that the substrate still binds, or that the substrate now fails to bind to the altered enzyme? Explain. ii) Choose an amino acid substitution for Ser 161. iii) Explain the possible outcome of this change. Note: There are many possible full-credit answers for (ii) and (iii). A table of amino acid structures can be found at the end of this exam. Question 3 a) Briefly define the following: Dominant: Recessive: Phenotype: Genotype: Alleles: Homozygous: Heterozygous: Mendel's First Law: Mendel's Second Law: Haploid: Diploid: b) A yeast cell has the genotype AaBb, where the A and the B loci are on different chromosomes. Sketch the chromosome arrangement of this cell in meiosis I, when 2n = 4
Question 4 you have started a UROP in the behavioral genetics department at the University of Monterrey in Mexico. For your first assignment, your advisor asks you to figure out the genetics of a particular species of honeybee that has just been discovered- a red killer To begin your studies, you cross this true breeding red killer bee with the local true breeding blue gentle bee. The Fl progeny show the following phenotype misTy you have characterized the disposition as such gentle: will ignore he d simply gather poller killer:will attack and sting without provocation feisty: will approach humans threateningly, but will not sting n)Write the genotypes of the Fo parental types and the F1 progeny (Be sure to indicate which particular phenotype corresponds to each parental genotype. Use H"and"h"as your symbols for the alleles of the gene conveying color or hue and"D and d"as your symbols for alleles of the gene for disposition Fo F1 b)you want to determine if the gene for hue is linked to the gene involved in disposition you decide to set up a test cross for the F1. Indicate the genotypes of the strains you choose for the cross c)Using your chosen strains indicate the ratio of genotypes and phenotypes of the progeny if the traits are not linked 5
5 Question 4 You have started a UROP in the behavioral genetics department at the University of Monterrey in Mexico. For your first assignment, your advisor asks you to figure out the genetics of a particular species of honeybee that has just been discovered- a red killer bee! To begin your studies, you cross this true breeding red killer bee with the local true breeding blue gentle bee. The F1 progeny show the following phenotype: 54 red "feisty" bees You have characterized the disposition as such: gentle: will ignore humans and simply gather pollen killer: will attack and sting without provocation feisty: will approach humans threateningly, but will not sting a) Write the genotypes of the F0 parental types and the F1 progeny. (Be sure to indicate which particular phenotype corresponds to each parental genotype.) Use "H" and "h" as your symbols for the alleles of the gene conveying color or hue and "D and d" as your symbols for alleles of the gene for disposition. F0 F1 b) You want to determine if the gene for hue is linked to the gene involved in disposition. You decide to set up a test cross for the F1. Indicate the genotypes of the strains you choose for the cross: c) Using your chosen strains indicate the ratio of genotypes and phenotypes of the progeny if the traits are NOT linked
uestion 5 In the following pedigree, assume no outsiders marrying in carry a disease allele #4 #2 #3 #5 a)what is the mode of inheritance of this disease? circle one Autosomal dominant Autosomal recessive X-linked dominant y-linked mitochondrial inheritance X-linked recessive b)Explain your choice in a). (Give two lines of reasoning. c)Write the genotypes of the following individuals (If more than one genotype is possible, write down all the possibilities. d)Name a disease that follows this pattern of inheritance e)What is the probability that the asterisked individual will be affected with the disease if male? if female? 6
6 Question 5 In the following pedigree, assume no outsiders marrying in carry a disease allele. ? * a) What is the mode of inheritance of this disease? Circle one. Autosomal dominant Autosomal recessive X-linked dominant Y-linked mitochondrial inheritance X-linked recessive b) Explain your choice in a). (Give two lines of reasoning.) c) Write the genotypes of the following individuals. (If more than one genotype is possible, write down all the possibilities.) #1________ #2________ #3________ #4_________ # 5________ d) Name a disease that follows this pattern of inheritance. e) What is the probability that the asterisked individual will be affected with the disease if male?______________ if female?______________ #1 #4 #2 #3 #5
Question 6 A long time ago, in a galaxy far far away, you are a scientist. you have just joined a lab that recently published a paper in Galactic Scientific reporting a new microorganism named Metachlorianus forcus, called metachlorians. These microorganisms colonize the brains of most humanoids. However, in those who are part of the religious sect known as the Jedi, they are found in very high concentrations. In Jedi, these microorganisms secrete a protein known as Saberin Saberin is encoded by the gene saberin. Saberin, when released in the brain, makes the Jedi emanate a sword known to many as a light saber blue is the most common light saber color amongst the jedi you would like to understand this phenomenon. First, you study the metachlorians. Like present day yeast cells, the metachlorians can live in both a diploid and haploid state. Knowing this, you can now study the genetics of the light saber phenomenon The assay you mutagenize haploid metachlorians and isolate mutants altered in the light saber phenomenon. The way you are going to look for mutants is by injecting mutagenized strains into the brain of a willing Jedi, Jacensolo, who has been depleted of his own metachlorians Because the strains you will inject are growth impaired, they stay around only long enough for jacensolo to make one light saber. This allows you to follow the protocol shown Inject mutant strain of metachlorians into the brain of jacensolo Allow Jacensolo to make a light saber Check light saber color for non-blue colors Let the injected metachlorians die off Inject a new mutant strain In this procedure, you isolate 10 mutants: m1, m2, m3, m4, m5, m6, m7, m8, m9 and m10. All of these mutants cause Jacensolo to create light sabers that are not blue The first thing you do is to find out how many complementation groups exist. So, you make diploid combinations between each of the mutants. you then inject these diploids into jacensolo and see if he produces a blue(WT)light saber. The results are shown below (+)=Blue light saber (-) non-blue light saber ml m2 m3 m4 m5 m6 m7 m8 m9 m10 wt m10 7
7 Question 6 A long time ago, in a galaxy far, far away, you are a scientist. You have just joined a lab that recently published a paper in Galactic Scientific reporting a new microorganism named Metachlorianus forcus, called metachlorians. These microorganisms colonize the brains of most humanoids. However, in those who are part of the religious sect known as the Jedi, they are found in very high concentrations. In Jedi, these microorganisms secrete a protein known as Saberin. Saberin is encoded by the gene saberin. Saberin, when released in the brain, makes the Jedi emanate a sword known to many as a light saber. Blue is the most common light saber color amongst the Jedi. You would like to understand this phenomenon. First, you study the metachlorians. Like present day yeast cells, the metachlorians can live in both a diploid and haploid state. Knowing this, you can now study the genetics of the light saber phenomenon. The assay: You mutagenize haploid metachlorians and isolate mutants altered in the light saber phenomenon. The way you are going to look for mutants is by injecting mutagenized strains into the brain of a willing Jedi, Jacensolo, who has been depleted of his own metachlorians. Because the strains you will inject are growth impaired, they stay around only long enough for Jacensolo to make one light saber. This allows you to follow the protocol shown: • Inject mutant strain of metachlorians into the brain of Jacensolo • Allow Jacensolo to make a light saber • Check light saber color for non-blue colors • Let the injected metachlorians die off • Inject a new mutant strain In this procedure, you isolate 10 mutants: m1, m2, m3, m4, m5, m6, m7, m8, m9 and m10. All of these mutants cause Jacensolo to create light sabers that are not blue. The first thing you do is to find out how many complementation groups exist. So, you make diploid combinations between each of the mutants. You then inject these diploids into Jacensolo and see if he produces a blue (WT) light saber. The results are shown below: (+) = Blue light saber (-) = non-blue light saber m1 m2 m3 m4 m5 m6 m7 m8 m9 m10 wt m1 --- --- +++ +++ +++ +++ --- +++ +++ --- +++ m2 --- +++ +++ +++ +++ --- +++ +++ --- +++ m3 --- +++ +++ --- +++ --- +++ --- +++ m4 --- --- +++ +++ +++ --- --- +++ m5 --- +++ +++ +++ --- --- +++ m6 --- +++ --- +++ --- +++ m7 --- +++ +++ --- +++ m8 --- +++ --- +++ m9 --- --- +++ m10 --- ---
a) How many complementation groups exist in your collection of mutants? b)How many ge enes have you found involved with this phenomenon? c)Designate your complementation groups A, B, C, D, E, F.and so on ( Put m1 into Group A). Which mutants are in each of your complementation groups? Now you want to find out the order in which these genes' products are acting. you do this by constructing haploid metachlorians with 2 mutations. The results of this analysis are shown m1m2Red‖m2m3 yellow m3 m4: yellow m4m5 Green m5m6yelw‖m6 m7: yellow‖m7m8yeow‖lm8m9 Yellow m1 m3: yellow2m4iRed‖m3m5 yellow‖m4m6 yellow‖hm5mv:Red‖m6m8 yellow‖m7m9Red m1m4:Red‖m2m5Red‖m3m6 yellow‖m4mRed‖m5 m8: yellow‖m6m9 yellow 1m5Red‖m2m6 yellow‖m3 m7: yellow m4mi: yellow‖m5m96r m1m6: yellow‖m2m7Red‖m3 m8: yellow‖m4m9:6ren m1m7iRed‖m2m8! yellow‖m3m9: yellow m1 m8: yellow‖mn2m9iRed m1 m9: Red d)What do you call this kind of analysis? e)Draw the light saber color pathway below Example nzY orange→ pt urpLe black h) Luke Skywalker made a green light saber. Explain this observation in terms of the metachlorians in his bod 8
8 a) How many complementation groups exist in your collection of mutants? ___________ b) How many genes have you found involved with this phenomenon? ______________ c) Designate your complementation groups A, B, C, D, E, F,… and so on. (Put m1 into Group A). Which mutants are in each of your complementation groups? Now you want to find out the order in which these genes’ products are acting. You do this by constructing haploid metachlorians with 2 mutations. The results of this analysis are shown. Double mutant Sword color Double mutant Sword color Double mutant Sword color Double mutant Sword color Double mutant Sword color Double mutant Sword color Double mutant Sword color Double mutant Sword color m1 m2 Red m2 m3 Yellow m3 m4 Yellow m4 m5 Green m5 m6 Yellow m6 m7 Yellow m7 m8 Yellow m8 m9 Yellow m1 m3 Yellow m2 m4 Red m3 m5 Yellow m4 m6 Yellow m5 m7 Red m6 m8 Yellow m7 m9 Red m1 m4 Red m2 m5 Red m3 m6 Yellow m4 m7 Red m5 m8 Yellow m6 m9 Yellow m1 m5 Red m2 m6 Yellow m3 m7 Yellow m4 m8 Yellow m5 m9 Green m1 m6 Yellow m2 m7 Red m3 m8 Yellow m4 m9 Green m1 m7 Red m2 m8 Yellow m3 m9 Yellow m1 m8 Yellow m2 m9 Red m1 m9 Red d) What do you call this kind of analysis? _________________________ e) Draw the light saber color pathway below: Example: enzX enzY Orange purple black h) Luke Skywalker made a green light saber. Explain this observation in terms of the metachlorians in his body
STRUCTURES OF AMINO ACIDS -CH,CH,CH NH, H-C—CH, ALANInE ARGININE ASPARAGINE ASPARTIC ACID H-C—CH,-SH -CH,CH, H-C-CH,CH H-C-H H3 CYSTEINE GLUTAMIC ACID GLUTAMINE GLYCINE (cys) (glu) (gIN) (gly) H-C-C-CH CH3 H-C-CH2-C--CH3 H-C-CH CH CH2CH2-NH3 NH3 CH3 LYSINE HISTIDINE ISOLEUCINE LEUCINE (his) CH,CH H3 H-C-CH H-C-CH,-OH METHIONINE (met PHENYLALANINE SERINE (phe PROLINE (ser) H-C-CH, -CH -C-CH H→ H3 THREONINE TRYPTOPHAN/ VALINE (thr) (trp TYROSINE (val)
9 ALANINE (ala) ARGININE (arg) ASPARAGINE (asN) C C O O H NH3 CH3 - + C C O O H NH3 C H CH3 CH3 - + C C O O H NH3 CH2CH2CH2 N H C NH2 NH2 - + + C C O O H NH3 CH2 C O NH2 - + C C O O H NH3 CH2 C O O - + - ASPARTIC ACID (asp) C C O O H NH3 CH2 SH - + CYSTEINE (cys) C C O O H NH3 CH2CH2 O O C - + - C C O O H NH3 CH2CH2 O C NH2 - + C C O O H NH3 H - + C C O O H NH3 CH2 C N C N H H H H - + + C C O O H NH3 C H CH3 CH2CH3 - + C C O O H NH3 CH2 C H CH3 CH3 - + C C O O H NH3 CH2CH2CH2CH2 NH3 + - + C C O O H NH3 CH2CH2 S CH3 - + C C O O H NH3 CH2 H H H H H - + C N CH2 CH2 CH2 H H H - C O O + C C O O H NH3 CH2 OH - + C C O O H NH3 C H OH CH3 - + C C O O H NH3 CH2 - + C C O O H NH3 CH2 OH H H H H - + GLUTAMIC ACID (glu) GLUTAMINE (glN) GLYCINE (gly) HISTIDINE (his) ISOLEUCINE (ile) LEUCINE (leu) LYSINE (lys) METHIONINE (met) PHENYLALANINE (phe) PROLINE (pro) SERINE (ser) THREONINE (thr) TRYPTOPHAN (trp) TYROSINE (tyr) VALINE (val) STRUCTURES OF AMINO ACIDS C N H H H H H H
Solutions to Practice Quiz 1 1) a)most hydrophob b)intermediate tyrosine c)least hydrophobic threonine d)Phe is more hydrophobic than tyr because tyr has a hydrophilic-OH group that phe lacks(-OH can form H-bonds) e) tyr is more hydrophobic than thr because, although both have -,'s, tyr has more non-polar Ch's than thr 2) a) hydrogen and ionic bonds(vdw OK but not required) b) i) hydrogen bond(vdw OK but not required) i) H C indicates the connections to the backbone) c)iIt should still bind because the lys is also(+)charged and can therefore still make an ionic with the(-)of the phosphate i)and ii) Determine if your substitution changes the ability of the enzyme and substrate to form a hydrogen bond. If it does, is that interaction now stronger or weaker? For example, if Ser 161 was changed to Ala, the ability to form a hydrogen bond would be lost. Therefore the interaction is weaker, and you may predict that the substrate no longer binds Dominant: Phenotype 1 is dominant over phenotype 2 if the F1 heterozygote of the two alleles shows phenotype 1. Recessive: Phenotype 2 in the above example above is recessive. In other words,a recessive phenotype is only visible when the recessive alleles are homozygous Phenotype: An observed characteristic of an individual that develops under the influence of one or more genes and the environment. Any trait that can be measured is a phenotype Genotype: The description of a genetic makeup of an individual, in terms of what alleles it has for one or more ge Alleles: Alternative forms of a gene
10 Solutions to Practice Quiz 1 1) a) most hydrophobic: phenylalanine b) intermediate tyrosine c) least hydrophobic threonine d) Phe is more hydrophobic than tyr because tyr has a hydrophilic -OH group that phe lacks (-OH can form H-bonds). e) tyr is more hydrophobic than thr because, although both have -OH’s, tyr has more non-polar CH’s than thr. 2) a) hydrogen and ionic bonds (vdw OK but not required). b) i) hydrogen bond (vdw OK but not required). CH2 C H NH * C O * O H O O * * P ii) (* indicates the connections to the backbone) c) i) It should still bind because the lys is also (+) charged and can therefore still make an ionic with the (-) of the phosphate. ii) and iii) Determine if your substitution changes the ability of the enzyme and substrate to form a hydrogen bond. If it does, is that interaction now stronger or weaker? For example, if Ser 161 was changed to Ala, the ability to form a hydrogen bond would be lost. Therefore the interaction is weaker, and you may predict that the substrate no longer binds. 3) Dominant: Phenotype 1 is dominant over phenotype 2 if the F1 heterozygote of the two alleles shows phenotype 1. Recessive: Phenotype 2 in the above example above is recessive. In other words, a recessive phenotype is only visible when the recessive alleles are homozygous. Phenotype: An observed characteristic of an individual that develops under the influence of one or more genes and the environment. Any trait that can be measured is a phenotype. Genotype: The description of a genetic makeup of an individual, in terms of what alleles it has for one or more genes. Alleles: Alternative forms of a gene
