Human Heredity Principles and Issues

10th Edition Michael Cummings

Solutions Manual
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 10
FROM PROTEINS TO PHENOTYPES
CHAPTER OUTLINE
PROTEINS ARE THE LINK BETWEEN DEFECTS IN TRANSPORT PROTEINS:
GENES AND THE PHENOTYPE HEMOGLOBIN
ENZYMES AND METABOLIC Sickle cell anemia is an autosomal
PATHWAYS recessive disorder.
PHENYLKETONURIA: A MUTATION Thalassemias are also inherited
THAT AFFECTS AN ENZYME hemoglobin disorders.
How is the metabolism of Hemoglobin disorders can be treated
phenylalanine related to PKU? through gene switching.
PKU can be treated with a diet low in PHARMACOGENETICS
phenylalanine. Taste and smell differences: We live in
How long must a PKU diet be different sensory worlds.
maintained? Drug sensitivities are genetic traits.
What happens when women with ECOGENETICS
PKU have children of their own? What is ecogenetics?
OTHER METABOLIC DISORDERS IN THE Sensitivity to pesticides varies widely
PHENYLALANINE PATHWAY in different populations.
GENES AND ENZYMES OF GENETIC JOURNEYS—Dietary
CARBOHYDRATE METABOLISM Management and Metabolic Disorders
Galactosemia is caused by an enzyme GENETIC JOURNEYS—The First Molecular
deficiency. Disease
Lactose intolerance is a genetic SPOTLIGHT ON . . . Why Wrinkled Peas
variation. Are Wrinkled
MUTATIONS IN RECEPTOR PROTEINS SPOTLIGHT ON . . . Population Genetics of
Sickle Cell Genes

CHAPTER SUMMARY
This chapter opens with a vignette about the discovery of phenylketonuria that reinforces the
relationship between gene products and phenotype. The role of proteins as the link between
genotype and phenotype is described.

To begin the discussion of metabolic disease, the great variety of protein functions and possible
protein structures are described. Enzyme function is defined, metabolic pathways are described
and Archibald Garrod’s elucidation of alkaptonuria is recalled. To illustrate the role of enzymes
as gene products in the production of phenotype, defects in pathways of amino acid

86 Chapter Ten
metabolism are used as examples. Figure 10.4 summarizes the metabolic pathways that begin
with phenylalanine, and shows several genetic disorders associated with metabolic blocks and
their phenotypic consequences. Phenylketonuria (PKU) is used as a classic example of a
metabolic block that has phenotypic consequences as a result of the accumulation of products in
a secondary pathway. Its progress and treatment are described at length. This is contrasted with
genetic goitrous cretinism, another condition associated with phenylalanine metabolism, but in
which phenotypic consequences result from lack of an important pathway product.

Basic carbohydrate chemistry is summarized as a lead-in to a discussion of defects in

carbohydrate metabolism. One such defect, galactosemia, is caused by lack of an enzyme and
can be incompletely corrected by diet. Another more common condition, lactose intolerance, is
described as a variation in gene expression.

A brief section on mutations in receptor proteins recalls earlier discussions of androgen

insensitivity and familial hypercholesterolemia as examples of conditions caused by such
defects.

Defects in proteins that function in transport are also covered, using the various hemoglobin
abnormalities as examples. The hemoglobin molecule and the two hemoglobin gene clusters are
described as background to discussion of hemoglobin variants. In this section the point is made
that the defect in sickle cell anemia is caused by the substitution of one out of 146 amino acids in
the structure of beta globin. This is done to provide a graphic example of the relationship
between the nucleotide sequence of a gene, the amino acid sequence of a protein, and the
phenotype. Thalassemias and other variants are described. The section ends with an account of
the novel method of gene switching to treat these disorders.

A section on pharmacogenetics introduces the concept that we live in greatly different sensory
worlds due to genetic differences in our abilities to taste or smell various compounds. This in
turn likely affects our chosen diets and therefore our health. Genetic differences also exist that
cause potentially lethal sensitivity to various drugs; two examples are described.

In the last section, ecogenetics is defined as the branch of pharmacogenetics dealing with
sensitivity to environmental chemicals. A gene whose alleles provide varying degrees of
resistance to both a common insecticide and a toxic nerve gas agent is discussed.

TEACHING/LEARNING OBJECTIVES
By the conclusion of this chapter, students should have a thorough understanding of:
a. The concept that proteins are the end products of genes.
b. The fact that proteins that function as enzymes participate in metabolic pathways.
c. The idea that mutations can produce defects in enzymes that affect metabolic pathways,
producing phenotypic effects due to either lack of a necessary product or accumulation
of a toxic pathway substance; details of PKU provide a useful example.
d. The functional capacities of proteins in other roles, including receptors and transport.

From Proteins to Phenotypes 87

 e. The phenotypic effects of mutations that affect the amino acid sequence of receptor
proteins, and of transport proteins such as the hemoglobin defects sickle cell anemia and
the thalassemias.
f. The role of gene differences in pharmacogenetics and ecogenetics.

TERMS DEFINED IN THIS CHAPTER

• Substrate: The specific chemical compound that is acted upon by an enzyme.
• Product: The specific chemical compound that is the result of enzyme action. In
biochemical pathways, a compound can serve as the product of one reaction, and the
substrate for the next reaction.
• Metabolism: The sum of all biochemical reactions by which cells convert and utilize
energy.
• Alkaptonuria: A relatively benign autosomal recessive genetic disorder associated with
the excretion of high levels of homogentisic acid.
• Inborn error of metabolism: The concept advanced by Archibald Garrod that many
genetic traits are the result of alterations in biochemical pathways.
• Essential amino acids: Amino acids that cannot be synthesized in the body and must be
supplied in the diet.
• Phenylketonuria (PKU): An autosomal recessive disorder of amino acid metabolism
that results in mental retardation if untreated.
• Galactosemia: A heritable trait associated with the inability to metabolize the sugar
galactose. Left untreated, high levels of galactose-1-phosphate accumulate, causing
cataracts and mental retardation.
• Lactose intolerance: An autosomal recessive genetic trait associated with decline of
activity of the enzyme lactase in adults, resulting in intolerance to dairy products.
• Pseudogenes: Nonfunctional genes that are closely related (by DNA sequence) to
functional genes present elsewhere in the genome.
• Hemoglobin variants: Alpha and beta globins with variant amino acid sequences.
• Thalassemias: Genetic disorders associated with an imbalance in the ratio of alpha and
beta globin.
• Alpha thalassemia: Genetic disorder associated with an imbalance in the ratio of alpha
and beta globin caused by reduced or absent synthesis of alpha globin.
• Beta thalassemia: Genetic disorder associated with an imbalance in the ratio of alpha
and beta globin caused by reduced or absent synthesis of beta globin.
• Pharmacogenetics: A branch of genetics that is concerned with the inheritance of
differences in the response to drugs.

88 Chapter Ten
 • Ecogenetics: A branch of genetics that studies genetic traits related to the response to
environmental substances.

TEACHING HINTS
In a definition in a previous chapter and in Table 10.3 the author describes familial
hypercholesterolemia as dominant, and in this chapter thalassemia is defined as recessive, even
though in both cases the heterozygote has markedly milder symptoms than the homozygote. As
in chapter 5, this brings up the fuzziness of these terms and the need, perhaps, to point this out
to students.

Lactose intolerance is a fairly common condition and fairly well known, thanks to advertising.
Students often confuse this with galactosemia since in both cases milk and dairy product
consumption is a problem. It might be a good idea to specifically make sure students
understand the difference.

Even if there is no lab in your course, the PTC tasting test is a popular exercise with students.
Sensitive tasters are astounded that others cannot detect what to them is an obvious and terrible
taste. Although use of one-strength test papers is easy and cheap, use of varied-strength
solutions is both more informative, as the text points out, and also saves sensitive tasters a very
unpleasant experience if they test themselves starting with the weakest solution.

Ask students to notice the “WARNING: CONTAINS PHENYLALANINE” printed on packs of

NutraSweet and other brands of aspartame. Point out that they now understand the reason for
the warning, and ask how many of them ever noticed it before, or would have realized its
purpose.

VIDEOS, WEBSITES, AND ANIMATIONS

VIDEOS
YouTube — Enzyme Basics
A basic anatomical view of the actions of enzymes in our bodies.
http://www.youtube.com/watch?v=AFbPHlhI13g

Vimeo — Introduction to Metabolism

Video lecture on metabolism. Contains links to other lecture videos on other aspects of
metabolism.
http://vimeo.com/4062325

Evolution Series —A Mutation Story

PBS video depicting the evolutionary aspects of sickle cell anemia.
http://www.pbs.org/wgbh/evolution/library/01/2/l_012_02.html

From Proteins to Phenotypes 89

WEBSITES
PubMed Health — Phenylketonuria
Website for information on phenylketonuria.
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002150/

National PKU News

News and information about phenylketonuria. Includes information for research, personal
stories, and related links.
http://www.pkunews.org/

PKU
Online resource and support group for those with PKU and parents of children with PKU.
http://www.pku.com/

MedScape Reference — Inborn Errors of Metabolism

Medical website with extensive treatment of IEMs.
http://emedicine.medscape.com/article/804757-overview

Metabolism: Clinical and Experimental

Link to the scientific journal. Requires subscription. Articles may be purchased separately. Free
trial issue.
http://www.metabolismjournal.com/

Genetics Home Reference — Galactosemia

Article on the genetics of galactosemia with links for further information.
http://ghr.nlm.nih.gov/condition/galactosemia

Genetic Disease Profile: Sickle Cell Anemia

Overview of sickle cell anemia with related timeline and a number of useful links.
http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/sca.shtml

Pharmacogenetics and Genomics

Scientific journal. Requires subscription. Articles may be purchased separately.
http://journals.lww.com/jpharmacogenetics/pages/default.aspx

Nuffield Council on Bioethics — Pharmacogenetics

Downloadable PDF report on the ethics and implications of pharmacogenetics.
http://www.nuffieldbioethics.org/pharmacogenetics

Center for Ecogenetics and Environmental Health at the University of Washington

Organization aimed at researching relationship between genetics and our susceptibility to
environmental health risks.
http://depts.washington.edu/ceeh/

90 Chapter Ten
Ecogenetics, Evolutionary Biology, Genomics, and Medicine
Downloadable PowerPoint presentation from conference on Darwin and medicine.
www.pitt.edu/~super7/32011-33001/32211-32221.ppt

ANIMATIONS
Biological Animations
Short animations of biological processes including enzyme activity and metabolism.
http://www.stolaf.edu/people/giannini/biological%20anamations.html

KScience — Enzymes
Animation with an interactive that allows changing parameters to investigate how enzymes act
under varying conditions. Downloadable files.
http://www.kscience.co.uk/animations/anim_2.htm#top

Learners TV — Biology Animations

A host of animations on various aspects of biological processes including enzyme activity and
metabolism.
http://www.learnerstv.com/animation/Free-biology-animations-page1.htm

ANSWERS TO TEXT QUESTIONS

1. The mother’s metabolism can compensate for the defect.

2. Accumulation of one or more precursors may be detrimental. Overuse of an alternative

minor pathway may result in the accumulation of toxic intermediates. Deficiency of an
important product may occur. Other reactions may be blocked.

3. C

4. a. Buildup of substance A, no substance B or C

b. Buildup of substance B, no substance C
c. Buildup of substance B, as long as A is not limiting factor
d. 1/2 the amount of C

5. a. Yes. Each will carry the normal gene for the other enzyme. (Individual 1 will be
mutant for enzyme 1 but normal for enzyme 2. This is because enzyme 1 and 2 are
encoded by two different genes)
b. Let D = dominant mutation in enzyme 1, let normal allele = d
Let A = dominant mutation in enzyme 2, let normal allele = a
Ddaa X ddAa
Offspring: DdAa mutation in enzyme 1 and 2, A buildup, no C
Ddaa mutation in enzyme 1, A buildup, no C
ddAa mutation in enzyme 2, B buildup, no C

From Proteins to Phenotypes 91

 ddaa no mutation, normal
Ratio would be 1:2:1 for substance B buildup, no C: substance A buildup, no C: normal

6. Alleles for enzyme 1: A (dominant, 50% activity); a (recessive, 0% activity). Alleles for
enzyme 2: B (dominant, 50% activity); b (recessive, 0% activity).

Enzyme 1 Enzyme 2 Compound A Compound B Compound C

1AABB 100 100 N N N
2AaBB 50 100 N N N
4AaBb 50 50 N N N
2AABb 100 50 N N N
1AAbb 100 0 N B L
2Aabb 50 0 N B L
1aaBB 0 100 B L L
2aaBb 0 50 B L L
1aabb 0 50 B L L

N, normal; B, buildup; L, less.

7. a. 1 and 6; 2 and 7, 3 and 8. We know this because when 1 and 6 are mixed, they cannot
produce protein E because they contain defects in the same gene. The same is true for 2
and 7, 3 and 8. However, when 1 and 5 are combined, for example, protein E can be
made because 1 and 5 contain mutations in different genes.
b. Yes, individual 2 has a mutation in a different gene than individual 3.
c. No, individual 1 has a mutation in the same gene as individual 6.

8. 5, because the data shows that there are 5 groups of mutations (1 and 6, 2 and 7, 3 and 8, 4,
5) meaning that there are five different genes that are mutated corresponding to five steps in
the pathway.

9 & 10.
Substrate: A→B→C→D→E
Block for individuals: 5 2,7 1,6 3,8 4

11. a. 1/4 normal, 3/4 retarded

b. Of the children who could not produce E (and are retarded), 2/3 would build up A, 1/3
would build up D. Of all children from this mating, 1/4 would be normal, 1/2 would be
retarded and accumulate A, 1/4 will be retarded and accumulate D.

12. B

13. The disease: phenylketonuria (PKU), a deficiency of the enzyme phenylalanine hydroxylase.
This enzyme is used to convert the substrate phenylalanine to the product tyrosine.

92 Chapter Ten
 Phenotype: enhanced reflexes, convulsive seizures, and mental retardation; also, they have
lighter hair and skin color than siblings and other family members.

14. No. Essential amino acids are amino acids that the body cannot produce. Therefore, these
amino acids must be included in the diet. PKU sufferers can limit their phenylalanine intake
and prevent much of the mental retardation that would normally occur. If phenylalanine
were not an essential amino acid, the body would be able to produce it but would not be
able to convert it to tyrosine. This would lead to mental retardation. Therefore, a diet with
low phenylalanine levels would not have a significant effect.

15. Normal. Phenylketonuria and alkaptonuria are caused by mutations in different genes
affecting different enzymes. The children will be normal in phenotype because they will
carry one normal copy of the PKU gene, the phenylalanine hydroxylase gene, from the AKU
parent. Similarly, the children will have one normal copy of the AKU gene, the
homogentisic acid oxidase gene, from the PKU parent.

16. There was a failure in a biochemical reaction in the pathway prior to this step; therefore,
there was no substrate for the enzyme to work on.

17. No, because individuals who are GD/GD show 50 percent activity. The g allele reduces
activity by 50 percent so heterozygotes appear normal. It is not until the level of activity falls
below 50 percent that the mutant phenotype is observed.

18. Let H = the mutant allele for hypercholesterolemia

Let h = the normal allele
ANSWER: HH Heart attack as early as the age of 2, definite heart disease by age 20,
death in most cases by 30. No functional LDL receptors produced.
Hh Heart attack in early 30s. Half the number of functional receptors are
present and twice the normal levels of LDL.
Hh Normal. Both copies of the gene are normal and can produce functional
LDL receptors.

19. Gene therapy could be used, in which the normal gene is inserted into a vector and
delivered to the cells of the liver of a HH or Hh individual. If the gene gets into the liver
cells, it may express the normal receptor protein on the cell surface and remove LDL from
the circulatory system. Biotechnology (the production of the human LDL receptor and
injection into individuals) cannot be used. The LDL receptor has to be embedded in the cell
membrane and therefore has to essentially be “inside cells.” A human protein circulating in
the blood cannot spontaneously insert itself in the membrane of liver cells.

20. Disorder: androgen insensitivity. Without the ability to bind the hormone testosterone, a
complete change in the sexual phenotype results, causing a genotypic male (XY) to develop
into a phenotypic female.

From Proteins to Phenotypes 93

21. Hemoglobin has a complex quaternary structure in that it is composed of four polypeptide
chains: two alpha and two beta chains. These chains are each associated with a heme group.
Alpha and beta polypeptides are encoded by different genes located on different
chromosomes.

22. Beta thalassemia: caused by a defect in the conversion of pre-mRNA into a mature RNA
molecule. A mutation in one or more of the introns could have interfered with normal
mRNA splicing events, resulting in very low levels of functional mRNA and low level of
beta globin.

23. It would cause a frame shift mutation very early in the protein. Most likely, the protein
would lose all of its functional capacity.

24. Yes. If you mutate gene X, the protein will be nonfunctional and this will cause the mutant
phenotype. If you mutate the transcriptional regulator gene, the protein will be
nonfunctional and will not allow the transcription of gene X. In both cases, no normal gene
X protein is present and the mutant phenotype would be manifested.

25. One fourth will be normal. The other three fourths will be missing one, two, and three
copies of the gene, respectively, causing non-lethal alpha-thalassemia with varying degrees
of severity.

26. Drugs usually act on proteins. Different people have different forms of proteins. Different
proteins are inherited as different alleles of a gene.

27. People have different abilities to smell and taste chemical compounds such as
phenylthiocarbamide (PTC); some people are unable to smell skunk odors; different
reactions to succinylcholine, a muscle relaxant, and to primaquine, an antimalarial drug.
Others are sensitive to the pesticide parathion.

DISCUSSION OR SHORT ANSWER QUESTIONS

1. In Chapter 4, two forms of bleeder’s disease, hemophilia A and hemophilia B, were
described. Each is deficient in a clotting factor. What would you predict are the clotting
capacities of a mixture of blood from these two disorders? Why?

2. Certain traits in humans are incompletely penetrant, or show variations in expressivity.

Can you suggest a biochemical explanation for these observations in such cases caused by
a metabolic error?

3. In most cases, mutations in metabolic pathways produce a recessive trait. Suggest how a
mutation in a metabolic pathway might produce a dominant condition.

94 Chapter Ten
4. Why do you think some heterozygotes produce only half the normal amount of a given
enzyme and yet have a normal phenotype?

5. Why must dietary therapy for PKU be instituted soon after birth?

6. Show how the environment, extrauterine and intrauterine, can influence the expression of
PKU.
7. Discuss the various possible effects of the loss of the activity of an enzyme.

8. Discuss therapeutic approaches in metabolic diseases.

9. What does the chapter’s section on pharmacogenetics and ecogenetics tell us about the
issue of the relative safety of chemicals sold to the public and used in industry?

From Proteins to Phenotypes 95

Another random document with
no related content on Scribd:
Was certaine goods to England he had sold,
Which in the hands of creditors, but bad,
Small hope to get, yet lesser meanes he had.

68.

Hither his wants him forciblie constrain’d,

Though with long trauell both by land and seas,
Led by this hope, that only now remain’d,
Whereon his fortune finally he laies,
And if he found that friendship heere were fain’d,
Yet at the worst it better should him please,
Farre out of sight, to perish heere vnknowne,
Then vnrelieu’d be pitied of his owne.

69.

It chanc’d as I toward Westminster did ride,

’Mongst the great concourse passing to and fro,
An aged man I happily espide,
Whose outward looks much inward griefe did show,
Which made me note him, and the more I ey’d
Him, me thought more precisely I should know,
Reuoluing long, it came into my mind,
This was the man to me had been so kind:

70.

Was therewithall so ioyed with his sight,

(With the deare sight of his so reuerend face)
That I could scarcely keepe me from t’alight,
And in mine armes him openly embrace:[2066]
Weighing yet (well) what some imagine might,
He being a stranger, and the publike place
Checkt my affection, till some fitter hower
On him my loue effectually might shower.

71.
“Neuer,” quoth I, “was fortune so vniust
As to do wrong vnto thy noble[2067] hart,
What man so wicked could betray the trust
Of one so vpright, of so good desart?
And though obey necessitie thou must,
As when the great’st[2068] the same to me thou art,
Let me alone the last be left of all,
That from the rest declin’d not with thy fall.”

72.

And calling to a gentleman of mine,

Wise and discreet that well I knew to bee,
Shew’d him that stranger, whose deiected eyne
Fixt on the earth, nere once lookt vp at mee,
“Bid yonder man come home to me and dine”
Quoth I, “bespeake him reuerently, you see,
Scorne not his habit, little canst thou tell
How rich a mind in those meane rags doth dwell.”

73.

He with my name that kindly did him greete,

Slowly cast vp his deadly-mouing eye,
That long time had been fixed on his feete,
To looke no higher then his miserie,
Thinking him more calamitie did greete,
Or that I had supposed him some spye,
With a deepe sigh that from his heart he drew,
Quoth he: “His will accomplisht be by you.”

74.

My man departed, and the message done,

He whose sad heart with strange impressions strooke,
To thinke vpon this accident begun,
And on himselfe suspitiously to looke,
Into all doubts he fearefully doth run,
Oft himselfe cheering, oft himselfe forsooke:
Strangely perplext vnto[2069] my house doth come,
Not knowing why iudg’d, nor dreading yet his doome.

75.

My seruants set his comming to attend,

That were therein not common for their skill,
Whose vsage yet the former did amend:
He hop’d not good, nor guiltie was of ill,
But as a man whose thoughts were at an end:
“Fortune,” quoth he, “then worke on me thy will,
Wiser then man, I thinke, he were that knew
Whence this may come, or what thereof ensue.”

76.

His honored presence so did me enflame,

That though[2070] being then in presence of my peeres,
Daine not the lesse to[2071] meet him as he came,
(That very hardly could containe my teares)
Kindly salute him, call him by his name,
And oft together aske him how he cheares,
With still along maintaining the extreame:
Yet thought the man he[2072] had been in a dreame.

77.

At length t’awake[2073] him gently I began

With this demaund, if once he did not know
One Thomas Cromwell, a poore English man
By him relieu’d, when he was driuen low:
When I perceiu’d he my remembrance wan,
Yet with his teares it silently did show:
I wept for woe, to see mine host distrest,
But he for ioy to see his happie guest.
 78.

Him to the lords I publisht by my praise,

And at my table carefully him set,
Recounting them the many sundrie waies
I was vnto this gentleman[2074] in debt,
How great he was in Florence in those daies,
With all that grace or reuerence him might get:
Which all the while yet silently he heares,
Moisting among his viands with his teares.

79.

And to lend fulnesse lastly to his fate,

Great summes I gaue him, and what was his due
Made knowne, my selfe became his aduocate,
And at my charge his creditors I sue,
Recouering him vnto his former state:
Thus he the world began by me anew,
That shall to all posteritie expresse
His honored bountie, and my thankfulnesse.

80.

But muse recount, before thou further passe,

How this great change so quickly came about,
And what the cause of this sad downefall was,
In euery part the spatious realme throughout,
Being effected in so little space,
Leaue not thereof posteritie to doubt,
That with[2075] the world obscured else may bee,
If in this place reuealed not by thee.

81.

If the whole land did on the church relie,

Hauing full power kings to account to call,
That to the world read only policie,
Besides heauen’s keyes to stop or let in all,
Let me but know from her supremacie
How she should come so suddenly to fall:
’Twas more then chance sure put a hand thereto,
That had the power so great a thing to do.

82.

Or ought there were had biding vnder sunne,

Who would haue thought those edifices great,
Which first religion holily begunne,
The church approu’d, and wisdome richly seate,
Deuotion nourish’d, faith allowance wonne,
And all that them might any[2076] way compleate,
Should in their ruines lastly buried lie,
But that begun and ended from the skie?

83.

And the king late obedient to her lawes,

Against the clerke of Germany had writ,
As he that first stirr’d in the churche’s cause,
Against him greatliest that oppugned it,
And wan from her so gratefull an applause,
Then in her fauour chiefly that did sit,
That as the prop, whereon she only stai’th,
Him she instil’d Defender of the faith.

84.

But not their power, whose wisdomes them did place

In the first ranke, the oracles of state,
Who that opinion strongly did embrace,
Which through the land receiued was of late,
Then ought at all preuailed in this case,
O powerfull doome of vnauoided fate,
Whose depth not weake mortalitie can know,
Who can vphold what heauen will ouerthrow?
 85.

When time now vniuersally did show

The power to her peculiarly annex’d,
With most abundance then when she did flow,
Yet euery hower still prosp’rously she wex’d,
But the world poore did by loose riots grow,
Which serued as an excellent pretext,
And colour gaue to plucke her from her pride,
Whose only greatnesse suffred none beside.

86.

Likewise to that posteritie did doubt,

Those at the first not rightly did[2077] adore,
Their fathers that too credulous deuout
Vnto the church[2078] contributed their store,
And to recouer only went about
What their great zeale had lauished before,
On her a strong hand violently lai’d,
Preying on that they gaue for to be prai’d.

87.

And now the[2079] king set in a course so right,

Which I for him laboriously had tract,
(Who, till I learn’d him, did not know[2080] his might)
I still to prompt his power with me to act,
Into those secrets got so deepe a sight,
That nothing lastly to his furtherance lackt,
And by example plainly to him showne,
How all might now be easly ouerthrowne.[2081]

88.

In taking downe yet of this goodly frame

He suddenly not brake off euery band,
But tooke the power first from the papall name,
After, a while let the religion stand,
When limbe by limbe he daily did it lame,
First tooke a leg, and after tooke a hand,
Till the poore semblance of a bodie left,
But all should stay it, vtterly bereft.

89.

For if some abbey hapned void to fall

By death of him that the superiour was,
Gaine, that did first church libertie enthrall,
Only supreame, promoted to the place,
’Mongst many bad, the worst most times of all,
Vnder the colour of some other’s grace,
That by the slander, from his life should[2082] spring,
Into contempt it more and more might bring.

90.

This time from heauen when by the secret course,

Dissension vniuersally began,
(Preuailing as a planetarie sourse)
I’th’church belieuing, as Mahumitan,
When Luther first did those[2083] opinions nurse,
Much from great Rome in little space that wan,
It to this change so aptly did dispose,
From whose sad ruine ours so great arose.

91.

That heere that fabrique vtterly did faile,

Which powerfull fate had limited to time,
By whose strong law it naturally must quaile,
From that proud height to which it long did clime,
Letting ’gainst it the contrarie preuaile,
Therein to punish some notorious crime,
For which at length iust dooming heauen decreed,
 That on her buildings ruine heere should feed.

92.

Th’authoritie vpon her she did take,

And vse thereof in euery little thing,
Finding her selfe how oft she did forsake,
In her owne bounds her neuer limiting,[2084]
That awfull feare and due obedience brake
Which her reputed holinesse did bring,
From slight regard soone brought her into hate
With those that much disliked her[2085] estate.

93.

And that those[2086] parts she cunningly had plai’d,

Beliefe vnto her[2087] miracles to win,
Vnto the world[2088] were euery day bewrai’d,
From which the doubt did of her power begin,
Damnation yet to question what she said,
Made most suspect the faith they had been in,
When their saluation easly might be bought,
Found not this yet the way that they had sought.

94.

When those ill humours ripened to a head,

Bred by the ranknesse of the plentious land,
And they not only strangely from her fled,
Bound for her ancient libertie to stand,
But what their fathers gaue her being dead,
The sonnes rap’d from her with a violent hand,
And those her buildings most of all abus’d,
That with the waight their father’s coffins bruis’d.

95.
The wisest and most prouident but build,
For time againe too wastfully destroy,[2089]
The costly piles and monuments we guild,
Succeeding time shall reckon but a toy,
Vicissitude impartially wil’d,
The goodliest things be subiect to annoy,
And what one age did studiously maintaine,
The next againe accounteth vile and vaine.

96.

Yet time doth tell, in some things they did erre,

That put their helpe her brauery to deface,
When as the wealth, that taken was from her,
Others soone raised, that did them displace,
Their titles and their offices conferre
On such before, as were obscure and base,
Who would with her they likewise downe should go,
And o’rthrew them that her did ouerthrow.

97.

And th’Romish rites, that with a cleerer sight

The wisest thought they iustly did reiect,
They after saw that the receiued light,
Not altogether free was from defect,
Mysterious things being not conceiued right,
Thereof bred in the ignorant neglect,
For in opinion something short doth fall,
Wants there haue been, and shall be still in all.

98.

But negligent securitie and ease

Vnbridled sensualitie begat,
That only sought his appetite to please,
As in the midst it of abundance[2090] sat,
The church not willing others should her praise
That she was leane, when as her lands were fat,
Her selfe to too much libertie did giue,
Which some perceiu’d that in those times did liue.

99.

Pierce the wise plowman, in his vision saw

Conscience sore hurt, yet sorer was affraid
The seuen great sins to hell him like to draw,
And to wise clergie mainly cri’d for aid:
Falne ere he wist, whom perill much did awe,
On vncleane priests whil’st faintly he him staid,
Willing good clergie t’ease his wretched case,
Whom these strong giants hotly had in chase.

100.

Clergie call’d friers, which neere at hand did dwell,

And them requests to take in hand the cure,
But for their leechcraft that they could not well,
He listed not their dressing to endure,
When in his eare need softly him did tell
(And of his knowledge more did him assure)
They came for gain, their end which they did make,
For which on them the charge of soules they take.

101.

And voluntarie pouertie profest,

By food of angels seeming as to liue:
But yet with them th’accounted were the best
That most to their fraternitie doe giue,
And beyond number that they were increas’d:
“If so,” quoth Conscience, “thee may I beleeue,
Then t’is in vaine more on them to bestow,
If beyond number like they be to grow.”

102.
The frier soone feeling Conscience had him found,
And hearing how hypocrisie did thriue,
That many teachers euery where did wound,
For which Contriton miserably did grieue:
Now in deceit to shew himselfe profound,
His former hopes yet lastly so reuiue
Gets the pope’s letters, whereof he doth shape
Him a disguise from conscience to escape.

103.

And so towards goodly vnitie he goes,

A strong-built castle standing very hie,
Where Conscience liu’d to keepe him from his foes,
Whom, lest some watchfull centinell should spie,
And him vnto the[2091] garrison disclose,
His cowle about him carefully doth tie,
Creepes to the gate, and closely thereat beate,
As one that entrance gladly would intreate.

104.

Peace, the good porter, readie still at hand,

It doth vnpin, and praies him God to saue,
And after saluing, kindly, doth demand
What was his will, or who he there would haue?
The frier low lowting, crossing with his hand,
“T’speak with Contrition (quoth he) I would craue.”
“Father (quoth peace) your comming is in vaine,
For him of late hypocrisie hath slaine.”

105.

“God shield:” (quoth he) and turning vp the eyes,

“To former health I hope him to restore,
For in my skill his sound recouerie lies,
Doubt not thereof if setting God before:”
“Are you a surgeon?” Peace againe replies:
“Yea (quoth the frier) and sent to heale his sore:”
“Come neere (quoth Peace) and God your comming
speed,
Neuer of help contrition hath more need.”

106.

And for more haste he haleth in the frier,

And his lord conscience quickly of him told,
Who entertain’d him with right friendly cheere:
“O sir (quoth he) intreate you that I could
To lend your hand vnto my cosin deare[2092]
Contrition, whom a sore disease doth hold,
That wounded by hypocrisie of late,
Now lieth in most desperate estate.”

107.

“Sir (quoth the frier) I hope him soone to cure,

Which to your comfort quickly you shall see,
Will he a while my dressing but endure?”
And to Contrition therewith commeth hee,
And by faire speech himselfe of him assure,
But first of all going thorough for his fee:
Which done, quoth he: “If outwardly you show
Sound, ’tnot auailes if inwardly or no.”

108.

But secretly assoiling of his sin,

No other med’cine will vnto him lay,
Saying, that heauen his siluer him should win,
And to giue friers was better then to pray,
So he were shrieu’d what need he care a pin?
Thus with his patient he so long did play,
Vntill Contrition had forgot to weepe:
This the wise plowman shew’d me from his sleepe.
 109.

He saw their faults, that loosly liued then,

Others againe our weaknesses shall see:
For this is sure, he bideth not with men
That shall know all to be what they should bee:
Yet let the faithfull and industrious pen
Haue the due merit: but returne to mee,
Whose fall this while blind fortune did deuise,
To be as strange as strangely I did rise.

110.

Those secret foes yet subt’ly to deceiue,

That me maligning lifted at my state,
The king to marry forward still I heaue,
(His former wife being repudiate)
To Anne, the sister of the duke of Cleaue,
The German princes to confederate,
To backe me still ’gainst those against me lay,
Which as their owne retain’d me here in pay.

111.

Which my destruction principally wrought,

When afterward, abandoning her bed,
Which to his will to passe could not be brought,
So long as yet I beare about my head,
The only man her safetie that had sought,
Of her againe and only fauoured,
Which was the cause he hasted to my end,
Vpon whose fall her’s likewise did depend.

112.

For in his high distemp’rature of blood

Who was so great, whose life he did regard?
Or what was it that his desires withstood
He not inuested, were it nere so hard?
Nor held he me so absolutely good,
That though I crost him, yet I should be[2093] spar’d,
But with those things I lastly was to go,
Which he to ground did violently throw.

113.

When Winchester, with all those enemies,

Whom my much power from audience had debarr’d,
The longer time their mischiefes to deuise,
Feeling with me how lastly now it far’d,
When I had done the king that[2094] did suffice,
Lastly, thrust in against me to be heard,
When all[2095] was ill contrarily turn’d good,
Making amaine to th’shedding of my blood.

114.

And that the king his action doth deny,

And on my guilt doth altogether lay,
Hauing his riot satisfied thereby,
Seemes not to know how I therein did sway,
What late was truth conuerted heresie:[2096]
When he in me had purchased his pray,
Himselfe to cleere and satisfie the sin,
Leaues me but late his instrument therein.

115.

Those lawes I made, my selfe alone to please,

To giue me power more freely to my will,
Euen to my equals hurtfull sundrie waies,
(Forced to things that most do say were ill)
Vpon me now as violently ceaze,
By which I lastly perisht by my skill,
On mine owne necke returning (as my due)
 That heauie yoke wherein by me they drew.

116.

My greatnesse threatned by ill-boding eyes,

My actions strangely censured of all,
Yet in my way my giddines not sees
The pit, wherein I likely was to fall:
O were the sweets of man’s felicities
Often amongst not temp’red with some gall,
He would forget by his ore weening skill,
Iust heauen aboue doth censure good and ill.

117.

Things ouer rancke do neuer kindly beare,

As in the corne, the fluxure when we see
Fills but the straw, when it should feed the eare,
Rotting that time in ripening it should bee,
And being once downe it selfe can neuer reare:
With vs well doth this similie agree,
(By the wise man) due to the great in all,
By their owne weight being broken in their fall.

118.

Selfe-louing man what sooner doth abuse,

And more then his prosperitie doth wound?
Into the deepe but fall how can he chuse
That ouer-strides whereon his foot to ground?
Who sparingly prosperitie doth vse,
And to himselfe doth after-ill propound,
Vnto his height who happily doth clime,
Sits aboue fortune, and controlleth time.

119.

Not chusing that vs most delight doth bring,

And most that by the generall breath is freed,
Wooing that suffrage, but the vertuous thing,
Which in it selfe is excellent indeed,
Of which the depth and perfect managing
Amongst the most, but few there be that heed,
Affecting that agreeing with their blood,
Seldome enduring, neuer yet was good.[2097]

120.

But whil’st we striue too suddenly to rise

By flattring princes with a seruill tong,
And being soothers to their tyrannies,
Worke out more[2098] woes by what doth many wrong,
And vnto others tending iniuries,
Vnto our selues it hapneth oft among,
In our own snares vnluckily are caught,
Whil’st our attempts fall instantly to naught.

121.

The counsell chamber place of my arrest,

Where chiefe I was, when greatest was the store,
And had my speeches noted of the best,
That did them as hie oracles adore:
“A parliament was lastly my enquest,
That was my selfe a parliament before,
The Tower-hill scaffold last I did ascend:”
Thus the great’st man of England made his end.”

Michael Drayton.

FINIS.

END OF PART III.

 FOOTNOTES:
[1] To the. ed. 1559, 63.
[2] Many other of. 1559, 63.
[3] Heedy. 1559, 63.
[4] That there. 1559, 63.
[5] Officers. 1559, 63. Magistrates. 1575.
[6] Other places to shift of, and put by those that with flattery.
1559, 63.
[7] Offices. 1559, 63.
[8] To prank vp themselues. 1559, 63.
[9] Duties, and they wil geue more. 1559, 63.
[10] To bye them. 1559, 63.
[11] Seke only their commodity and ease. 1559, 63.
[12] Officers. 1559, 63.
[13] Officers. 1559, 63.
[14] When noughtye men had the regiment. 1559, 63.
[15] Our owne countrey. 1559, 63.
[16] ‘Folowing,’ not in editions 1559, 63.
[17] Deserued praises. 1559, 63, 75.
[18] Offices. 1559, 63. Officers, 1575.
[19] Scripture therfore calleth hypocrites, 1559, 63.
[20] Words within the parenthesis added 1571.
[21] A Mirrour for Magistrates can shewe, which therefore I
humbly. 1559, 63, 75.
[22] As in a loking glass. 1559. 63.
[23] Vice be in you. 1559, 63.
[24] Moue to the. 1559, 63.
[25] Chiefest ende whye it is. 1559, 63.
[26] God graunt it may attaine. 1559, 63, 75.
[27] But hyndred by the lorde chauncellor that then was. 1563.
—Stephen Gardiner, bishop of Winchester, made chancellor,
21 Sept. 1553, died Nov. 1555, and was succeeded as
chancellor, by Heath, archbishop of York, Wednesday, 1st
January, 1555.
[28] Of my lord Stafford. 1563.
[29] Although I haue bene called to another trade of lyfe, yet
my good lorde Stafford. 1563.
[30] Another parte, conteynyng as lytle of myne owne, as the
fyrst part doth of other men’s. Which, &c. 1563.
[31] The wurke was begun, and part of it printed IIII years
agoe, but hyndred by the lord chauncellour that then was,
nevertheles, through the meanes of my lord Stafford, lately
perused and licensed. Whan I first tooke it in hand, I had the
help of many graunted and offred of sum, but of few
perfourmed, skarce of any. So that when I entended to haue
continued it to quene Marie’s time, I haue ben faine to end it
much sooner: yet so, that it may stande for a patarne till the
rest be ready: which, with God’s grace, (if I may have anye
helpe) shall be shortly. In &c. 1559.
[32] Myrrour. 1559, 63.
[33] Enuyed and murdered. 1559, 63.
[34] Punish sinne boldly, bothe, &c. 1559. Suppres sinne,
1563.
[35] Lieutenauntes. 1559.
[36] Covet. 1559, 63.
[37] From edition, 1578.
[38] Lidgate’s booke of the fall. 1559, 63, 71.
[39] Hauinge made priuy thereto. 1578.
[40] Had abused here. 1578.
[41] For al men as well nobles as others to shewe. 1559, 63,
71.
[42] To enterprise, I refused vtterly alone to vndertake it,
without the helpe. 1578.
[43] Able to wield and discharge the weight of sutch a burden,
thinkinge. 1578.
[44] Diligent in hys affayres, procure me an Athlas to laye the
burden vppon my shoulders which I would not haue
undertaken, but that shortly after. 1578.
[45] In the first edition there only appears the productions of
Cavil, Churchyard, Ferrers, Phaer, Skelton and Baldwin.
[46] An. 1559, 63, 71, 75, 78.
[47] Wee did not mislyke. 1578.
[48] Cumlily. 1559; cumly. 1563.
[49] I maruayle, quod hee, what. 1578.
[50] Our nation, 1559, 63, 71, 78.
[51] Some also in the time of Bochas himselfe. 1578.
[52] Added in ed. 1571.
[53] Eyther by malice or misaduenture slaine in the new forest,
as he was in hunting there, by. 1575. Eyther by malice or
misaduenture slayne hunting in the new forest by. 1578.
[54] England, by Henry, &c. 1578.
[55] And after, myserably. 1578.
[56] Likewise, not in 1578.
[57] Henry the first, called Beauclerke, drowned vpon the sea
by the negligence of drunken mariners. 1578.
[58] The passage in brackets added in ed. 1571.
[59] Prosperity. The most vnnaturall murther of Artur, duke of
Britayne, right heyre of Englande, by king Ihon his vncle, with
the death of Isabell, his sister, by famyne. The myserable
ende of the sayd king Ihon their vncle, by surfet, or as some
write, poysoned by a monke of the abby of Swinsted in
Lyncolneshyre, are, &c. 1578.
[60] Wanted our countrey cronicles. 1559, 63.
[61] And a notable. 1559, 63.
[62] Supply. 1578.
[63] As blinde bayard is alway boldest. 1559, 63.
[64] Reigne. 1578.
[65] A time as troublesome to the people as vnlucky to the
prince 1578.
[66] Lewd meiney. 1576.
[67] And. 1559, 63.
[68] Although he be no great prynce: yet, &c. 1559, 63.
[69] And of other his fellowes learned in the law that were
plagued with him: thereby to warne all of theyr callinge and
profession, to beware of wrong judgementes. 1578.
[70] This preface is reprinted by Warton, as he says it cannot
easily be found. History of English Poetry, Vol. III. p. 217.
[71] In the present edition the original arrangement is
preserved.
[72] Anno 1388, added 1571.
[73] Sad. N.
[74] When as we. N.
[75] The lande. 1578.
[76] Vncorrupt and vpright, 1559, 63.
[77] Prynt it for a president. 1559, 63.
[78] Where judges. 1578.
[79] What fee is for falshoode. 1559, 63.
[80] Princes will. N.
[81] Who for filthy lucre, corrupt. 1578.
[82] Gainst justice wretchedly. N.
[83]

A chaunge more newe or straunge seldome hath be

seen,
Then from the benche above to cum downe to the bar;
Was never state so turned in no time as I ween,
As they to become clyents that counsaylours erst were:
But such is fortune’s play, which featly can prefer
The judge that sat above, full lowe beneth to stand,