Download Diabetes and the Central Dogma

Diabetes and the
Central Dogma
Students will learn about the central dogma of biology (DNA→RNA→Protein) by examining the
production and use of insulin and other regulatory hormones in the body and the ramifications
of those processes for society with respect to diabetes.
Author: Kenneth A. Gill
Port St. Lucie High School
Indian River State College
1
Contents
Introduction………………………………………………………….…………………………………………………3
Tips about the Curriculum……………………………………………………………………………………….4
Lesson Summaries…………………………………………………………………………………………………..5
Lesson Sequencing Summary………………………………………………………………………………….6
Master Vocabulary List…………………………………………………..………………………………………7–9
Next Generation Sunshine State Standards…………………………………..…………………….10–11
Lesson #1 – Pre-Test…………………………………………………………….................................12 – 13
Lesson #2 – Tour of the Basics
Teacher Pages……………………………………………………...…………………………………14–17
Student Pages………………………………………………………………………………………….18–19
Tour of the Basics Answer Key……………………….…………………………………………20–21
Lesson #3 - Diagnosing Diabetes
Teacher Pages ……………………………………………………………………………..………….22–27
Lesson #4 - Diabetes and the Central Dogma Powerpoint
Teacher Pages………………………………………………………………………………………….28–32
PowerPoint screenshots……………………………………………..……………………………34–39
Lesson #5 – From DNA to Protein Structure and Function
Teacher Pages ………………………………………...………………………………………………..40–44
Lesson #6 – Post-Test………………………………………………………………………………………………45–46
Pre/Post-Test Answer Key……………………..……………………………………………………………..…47–48
Acknowledgements……………………………………………………………………………………………………49
2
Introduction
The central dogma of molecular biology states in simple terms that genetic information for all
living organisms is contained in the nucleotide sequences of DNA, is transcribed by RNA and is then
translated into sequences of amino acids that become functional proteins. At least a rudimentary
understanding of this concept is a prerequisite to making sense of the nearly endless array of processes
that go on in living organisms. I have been trying, with varying degrees of success, to teach this to high
school biology students for nearly a decade but have not been satisfied with the outcomes. Many
concepts in biology can be visualized on a macro-scale, but the central dogma is not one of those
concepts and so must be visualized indirectly. Abstract concepts are often the hardest ones for
adolescents (or even adults) to grasp and trying to teach them completely abstractly is, I believe, the
root of my lack of success at teaching them.
Nearly everyone has a fear of, and/or a fascination with, disease. If a link can be demonstrated
between the symptoms of a disease and the production, or lack of production, of proteins it might be
possible to pique the interest of students in an otherwise dry and pedantic topic such as the central
dogma. Diabetes touches the lives of nearly everyone. With the near epidemic proportions of Type 2
diabetes in the United States and other developed nations most people either have it, are related to
someone that has it or at least know someone that has it. Depending on gender and ethnicity, the
average adult in the U.S. has a 30 to 40% probability of developing diabetes in their lifetime. Diabetes
comes in more than one form, is incompletely understood and is the focus of an enormous amount of
research. One thing that is understood, however, is that all forms of it involve the production, or lack of
production of certain proteins which leads us back to the central dogma. If the pedagogical approach to
the central dogma involves hanging it on a framework of a nearly ubiquitous disease such as diabetes
perhaps students will be more motivated to apply that part of their brain that processes the abstract.
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Tips about this Curriculum
Lesson Plan Format: All lessons in this curriculum unit are formatted in the same manner. In each lesson
you will find the following components:
KEY QUESTION(S): Identifies key questions the lesson will explore.
OVERALL TIME ESTIMATE: Indicates total amount of time needed for the lesson, including advanced
preparation.
LEARNING STYLES: Visual, auditory, and/or kinesthetic.
VOCABULARY: Lists key vocabulary terms used in the lesson. Also collected and defined in master
vocabulary list.
LESSON SUMMARY: Provides a 1-2 sentence summary of what the lesson will cover and how this
content will be covered. Collected in a master list.
STUDENT LEARNING OBJECTIVES: Focuses on what students will know, feel, or be able to do at the
conclusion of the lesson.
STANDARDS: Specific state benchmarks addressed in the lesson. Collected in a master list.
MATERIALS: Items needed to complete the lesson.
BACKGROUND INFORMATION: Provides accurate, up-to-date information from reliable sources about
the lesson topic.
ADVANCE PREPARATION: This section explains what needs to be done to get ready for the lesson.
PROCEDURE WITH TIME ESTIMATES: The procedure details the steps of implementation with suggested
time estimates. The times will likely vary depending on the class.
ASSESSMENT SUGGESTIONS: Formative assessment suggestions have been given. Additionally, there is a
brief summative assessment (pre/post test) that can be given. Teachers should feel free to create
additional formative and summative assessment pieces.
RESOURCES/REFERENCES: This curriculum is based heavily on primary sources. As resources and
references have been used in a lesson, their complete citation is included as well as a web link if
available. All references and resources are also collected in one list.
STUDENT PAGES: Worksheets and handouts to be copied and distributed to the students.
TEACHER PAGES: Versions of the student pages with answers or the activity materials for preparation.
SCIENCE SUBJECT: Biology
GRADE AND ABILITY LEVEL: Grades 9-12, Standard, Honors, International Baccalaureate
SCIENCE CONCEPTS: genetics, replication, transcription, translation, complementary base pairing,
mutation, nucleotide, nitrogenous base, DNA, hydrogen bonding, double helix, RNA, genes,
chromosomes, hormones, homeostasis, regulation, enzymatic function
OVERALL TIME ESTIMATE: Five 90 minute block periods
LEARNING STYLES: Visual, auditory, and kinesthetic
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Lesson Summaries
LESSON ONE: Pre-test/Post-test
This serves as both an elicitation of prior knowledge and a summative assessment of acquired
knowledge on the twin topics of diabetes and the central dogma. By presenting the same questions on
a two column sheet, students can demonstrate both to themselves and the teacher the outcomes of
their exposure to the other lessons.
LESSON TWO: Tour of the Basics
This lesson summarizes for the students the basic terms and concepts of the central dogma of biology
utilizing an animated, narrated website on the topic and accompanying student handout/worksheet.
LESSON THREE: Diagnosing Diabetes
Students sequence graphically presented information about the maintenance of blood sugar
homeostasis in both the healthy and diabetic person. Students analyze simulated blood plasma samples
collected during a glucose tolerance test for diabetes. They test glucose and insulin levels to determine if
the patient has Type 1 or Type 2 diabetes.
LESSON FOUR: Diabetes and the Central Dogma Powerpoint
This lesson is a straightforward exercise in transmitting content via powerpoint while students take
notes and are encouraged to ask questions based on the text and images they are seeing.
LESSON FIVE: From DNA to Protein Structure and Function
Students model how information in the DNA base sequence is transcribed and translated to produce a
protein molecule. They model how interaction between amino acids causes a protein to fold into a
three-dimensional shape that enables the protein to perform a specific function.
LESSON SIX (AND ONE): Pre-test/Post-test
This serves as both an elicitation of prior knowledge and a summative assessment of acquired
knowledge on the twin topics of diabetes and the central dogma. By presenting the same questions on
a two column sheet, students can demonstrate both to themselves and the teacher the outcomes of
their exposure to the other lessons.
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Lesson Sequencing Guide
Block 1
Pre-test
Tour of the
Basics internet
activity
Block 2
Diagnosing
Diabetes –
Introductory
discussion
Overview
Part 1
Part 2
Block 3
Diagnosing
Diabetes –
Part 3
Diabetes & The
Central Dogma
PowerPoint
Block 4
DNA to Protein
Structure and
Function
Introductory
discussion
Part A
Part B
Part C
Block 5
Wrap up
discussion
Post-test
Note: This sequencing summary is based on 90 minute block periods. As currently administered in our
district these occur every other day.
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Master Vocabulary List
Allele – one of two or more alternate forms of a gene
Ambiguity –the idea in reference to the genetic code that a particular codon might code for more than
one amino acid. This is not true of the genetic code, i.e., there is no ambiguity.
Amino acid – one of twenty monomers of proteins. Each of them have a central carbon atom
surrounded by an amine group, a carboxyl group, a hydrogen atom and a side group (referred to as the
“R-group” that is unique to each one.
Anti-codon – a group of three nitrogen bases found at one end of a transfer RNA that would be
complementary to a codon found on a messenger RNA
Blood plasma – the liquid component of blood. In humans approximately 1% of it consists of a variety
of solutes such as glucose, hormones, salts and the like
Central Dogma – more properly called a hypothesis, rather than a dogma, but it refers to the flow of
genetic information from DNA to RNA to proteins
Chromosome – a DNA molecule of varying length containing hundreds to thousands of genes and
usually found coiled around some histone proteins
Codon – a group of three nitrogen bases found in sequences of messenger RNA that code for a specific
amino acid
Complementary Base Pairing – an attraction between pairs of nitrogen bases found in nucleic acids
based on easily broken hydrogen bonds. Two of the five bases found in nucleic acids, adenine and
guanine are purines and they respectively bond with thymine and cytosine which are pyrimidines. In
RNA thymine is replaced by uracil, another pyrimidine
DNA – deoxyribonucleic acid, a molecule which is the main repository of genetic information in most
living organisms. It is a double-stranded polymer which assumes a helical shape and consists of
monomers of nucleotides which in turn consist of one deoxyribose sugar, one phosphate and one of
four nitrogen bases, adenine, guanine, cytosine and thymine
Degeneracy – the phenomenon that the genetic code is redundant, i.e., a given amino acid can be coded
for by more than one codon
Deletion – a form of genetic mutation wherein a nitrogen base is removed or left out thus leading to a
frame shift, i.e, the manner in which a sequence is read
Diabetes - group of similar disease states that in one way or another disrupt the body’s ability to
maintain homeostasis with respect to blood sugar levels. The two main forms would be:
Type 1 diabetes, wherein the pancreas fails to produce insulin, and
Type 2 diabetes, wherein there is a failure of the receptor proteins on multiple cell
surfaces that prevent insulin from promoting the uptake of glucose.
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Double Helix – the shape of a DNA molecule as postulated by Watson and Crick. It is like a twisted
ladder wherein the sides are constructed of alternating sugars and phosphates and the rungs of nitrogen
bases held weakly together by nitrogen bonds.
Enzyme – a protein that serves as an organic catalyst, i.e., it promotes biochemical reactions without
being consumed in them by lowering the activation energy required to make them go forward. Their
shape is critical to their function as there is an active site on them that conforms to the shape of the
substrate (reactants)
Exon – that part of a primary mRNA transcript that will actually serve as a source of coding to construct
the protein
Feedback Control Mechanisms - process in which the level of one substance influences the level of
another substance
Frame shift Mutation – a change in a gene sequence consisting of either an insertion or a deletion of a
nucleotide that from that point forward changes the manner in which the sequence will be transcribed
or translated
Gene – a sequence of nucleotides along one side of a DNA molecule that contains coded information for
a specific polypeptide
Genetics - the study of heredity and the variation of inherited characteristics
Glucose - A monosaccharide sugar, C6H12O6, occurring widely in most plant and animal tissue. It is the
principal circulating sugar in the blood and the major energy source of the body.
Hemoglobin - the oxygen-carrying pigment of red blood cells that gives them their red color and serves
to convey oxygen to the tissues
Heredity - the transmission of genetic characters from parents to offspring
Heterozygous – the condition in a diploid organism of having two different alleles for a particular trait
Homeostasis - the tendency of a system, especially the physiological system of higher animals, to
maintain internal stability, owing to the coordinated response of its parts to any situation or stimulus
that would tend to disturb its normal condition or function
Homozygous – the condition in a diploid organism of having two of the same allele for a particular trait
Hormone - any of various internally secreted compounds, as insulin or thyroxine, formed in endocrine
glands that affect the functions of specifically receptive organs or tissues when transported to them by
the body fluids
Hydrophilic – having an affinity for water
Hydrophobic – having a repulsion to water
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Insertion – a form of genetic mutation wherein a nucleotide is added to an existing sequence thus
leading to a frame shift, i.e., a change in the manner the sequence is transcribed or translated
Insulin - a polypeptide hormone, produced by the beta cells of the islets of Langerhans of the pancreas,
which regulates the metabolism of glucose and other nutrients.
Intron – a non-coding sequence within a primary mRNA transcript
Mutation – a change in a gene sequence
Nitrogen Base – nitrogen containing organic molecules found within the nucleic acids DNA and RNA that
have a weak affinity for one another and thus allow for complementary base pairing
Nucleotide – a monomer of the polymers DNA or RNA consisting of one sugar, one phosphate and one
of the nitrogen bases adenine, thymine, guanine, cytosine or uracil
Point Mutation – a change in a gene sequence of a single nucleotide
Polymer – a molecule consisting of a series of repeating similar units, or monomers. Examples would be
complex carbohydrates, proteins and nucleic acids
Polypeptide – a long, continuous and unbranched chain of amino acids held together by peptide bonds
Protein - large biological molecules consisting of one or more chains of amino acids that perform a vast
array of functions within living organisms
Protein Structure - the biomolecular structure of a protein molecule. Each protein is a polymer –
specifically a polypeptide – that is a sequence formed from various L-α-amino acids
Receptors – a molecule usually found on the surface of a cell that receives chemical signals from outside
the cell
Regulation – the process of turning genes on and off
Replication – the process of producing two identical DNA copies from one original DNA molecule
Trait - a distinct variant of a phenotypic character of an organism that may be inherited, be
environmentally determined or be a combination of the two
Transcription - the first step of gene expression, in which a particular segment of DNA is copied into RNA
by the enzyme, RNA polymerase
Translation - is the process in which cellular ribosomes create proteins. It is part of the process of gene
expression
Zygote – the initial cell resulting from the fertilization of an egg by a sperm
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Next Generation Sunshine State Standards (NGSSS)
S.C.912.N.1.1 Define a problem based on a specific body of knowledge, for example:
biology, chemistry, physics, and earth/space science, and do the following:
1. pose questions about the natural world,
2. conduct systematic observations,
3. examine books and other sources of information to see what is already known,
4. review what is known in light of empirical evidence,
5. plan investigations,
6. use tools to gather, analyze, and interpret data (this includes the use of measurement in metric and
other systems, and also the generation and interpretation of graphical representations of data, including
data tables
and graphs),
7. pose answers, explanations, or descriptions of events,
8. generate explanations that explicate or describe natural phenomena (inferences),
9. use appropriate evidence and reasoning to justify these explanations to others,
10. communicate results of scientific investigations, and
11. evaluate the merits of the explanations produced by others
S.C.912N1.3 Recognize that the strength or usefulness of a scientific claim is evaluated through
scientific argumentation , which depends on critical and logical thinking, and the active consideration of
alternative scientific explanations to explain the data presented.
S.C.912N1.4 Identify sources of information and assess their reliability according to the strict standards
of scientific investigation
S.C.912.N.3.1 Explain that a scientific theory is the culmination of many scientific investigations drawing
together current evidence concerning a substantial range of phenomena; thus, a scientific theory
represents the most powerful explanation scientists have to offer.
S.C.912.N.4.1 Explain how scientific knowledge and reasoning provide an empirically-based perspective
to inform society’s decision making.
SC.912.L.14.6 Explain the significance of genetic factors, environmental factors, and
pathogenic agents to health from the perspectives of both individual and public health.
S.C.912.L.14.30 Compare endocrine and neural controls of physiology
S.C.912.L.14.31 Describe the physiology of hormones including the different types and the mechanisms
of their actions.
S.C.912.L.14.46 Describe the physiology of the digestive system, including mechanical digestion,
chemical digestion, absorption and the neural and hormonal mechanisms of control.
SC.912.L.16.3 Describe the basic process of DNA replication and how it relates to the transmission and
conservation of the genetic information
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SC.912.L.16.4 Explain how mutations in the DNA sequence may or may not result in phenotypic change.
Explain how mutations in gametes may result in phenotypic changes in offspring.
S.C.912.L.16.5 Explain the basic processes of transcription and translation, and how the result in the
expression of genes.
S.C.912.L.16.6 Discuss the mechanisms for regulation of gene expression in prokaryotes and eukaryotes
at transcription and translation level
S.C.912.L16.8 Describe the relationship between mutation, cell cycle and uncontrolled cell growth
potentially resulting in cancer.
S.C.912.L.16.9 Explain how and why the genetic code is universal and is common to all organisms
SC.912.L.16.10 Evaluate the impact of biotechnology on the individual, society and the
environment, including medical and ethical issues.
SC.912.L.18.1 Describe the basic molecular structures and primary functions of the four major categories
of biological macromolecules.
SC.912.L.18.4 Describe the structures of proteins and amino acids. Explain the functions of proteins in
living organisms. Identify some reactions that amino acids undergo. Relate the structure and function of
enzymes.
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LESSON #1 – Pre-test
TIME ESTIMATE: 30 minutes
Pre-test
1. List at least five symptoms of diabetes.
2a. What is the principal organ involved in the development of diabetes?
2b. List 3 organs involved in long-term complications of diabetes.
3. As a member of the U.S. population what are the chances you will develop diabetes in your life
time?
A. 0-10%
B. 20-25%
C. 30-40%
D. 60-70%
4. Are you more likely to get Type 1 Diabetes or Type 2 Diabetes?
5. Compare and contrast Type 1 Diabetes and Type 2 Diabetes
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6. What, if any, is the relationship between DNA and Diabetes?
7. What, if any, is the relationship between DNA and proteins?
8. List at least 3 functions for proteins.
9. State, in as few words as possible, the central dogma of molecular biology.
10. What is a gene?
11. What is a mutation?
12. Name at least two possible outcomes of a genetic mutation.
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LESSON #2 – Tour of the Basics
KEY QUESTIONS: What structures and molecules in cells are involved in heredity and how do they work?
SCIENCE CONCEPTS: genetics, heredity, replication, transcription, translation
OVERALL TIME ESTIMATE: 60 minutes
LEARNING STYLES: Visual and auditory.
VOCABULARY:
Allele – one of two or more alternate forms of a gene
Chromosome – a DNA molecule of varying length containing hundreds to thousands of genes and
usually found coiled around some histone proteins
DNA – deoxyribonucleic acid, a molecule which is the main repository of genetic information in most
living organisms. It is a double-stranded polymer which assumes a helical shape and consists of
monomers of nucleotides which in turn consist of one deoxyribose sugar, one phosphate and one of
four nitrogen bases, adenine, guanine, cytosine and thymine
Gene – a sequence of nucleotides along one side of a DNA molecule that contains coded information for
a specific polypeptide
Hemoglobin - the oxygen-carrying pigment of red blood cells that gives them their red color and serves
to convey oxygen to the tissues
Heredity - the transmission of genetic characters from parents to offspring
Heterozygous – the condition in a diploid organism of having two different alleles for a particular trait
Homozygous – the condition in a diploid organism of having two of the same allele for a particular trait
Nucleotide – a monomer of the polymers DNA or RNA consisting of one sugar, one phosphate and one
of the nitrogen bases adenine, thymine, guanine, cytosine or uracil
Protein - large biological molecules consisting of one or more chains of amino acids that perform a vast
array of functions within living organisms
Replication – the process of producing two identical DNA copies from one original DNA molecule
Trait - a distinct variant of a phenotypic character of an organism that may be inherited, be
environmentally determined or be a combination of the two
Transcription - the first step of gene expression, in which a particular segment of DNA is copied into RNA
by the enzyme, RNA polymerase
Translation - is the process in which cellular ribosomes create proteins. It is part of the process of gene
expression
Zygote – the initial cell resulting from the fertilization of an egg by a sperm
LESSON SUMMARY: This lesson summarizes for the students the basic terms and concepts of the central
dogma of biology utilizing an animated, narrated website on the topic and accompanying student
handout/worksheet.
STUDENT LEARNING OBJECTIVE: Students should be able to:
1. Define the basic terminology of heredity at the organismic, cellular and molecular levels
2. Sequence the steps of the central dogma of biology
14
STANDARDS:
SC.912.L.16.3 Describe the basic process of DNA replication and how it relates to the transmission and
conservation of the genetic information
SC.912.L.16.4 Explain how mutations in the DNA sequence may or may not result in phenotypic change.
Explain how mutations in gametes may result in phenotypic changes in offspring.
S.C.912.L.16.5 Explain the basic processes of transcription and translation, and how they result in the
expression of genes.
S.C.912.L.16.6 Discuss the mechanisms for regulation of gene expression in prokaryotes and eukaryotes
at transcription and translation level
MATERIALS:
1. Internet source for each student or pair of students (laptop carts, computer lab, I-phones, etc.)
2. Comprehension worksheet for each student
BACKGROUND INFORMATION:
The central dogma of biology is an explanation of the flow of genetic information in living
organisms. The term central dogma is attributed to Francis Crick, one of the co-discoverers of the double
helix shape of DNA, who later acknowledged that his use of the term “dogma” was perhaps unfortunate
in that it implied a rigidity of thinking that would stand in opposition to the scientific method. More
than a half century of myriad lines of research have unequivocally confirmed, however, that information
contained in the nitrogen base sequences of DNA is transcribed on to RNA and then translated into
proteins. Genetic information is conserved from parent to progeny by the process of DNA replication
and, in some special cases involving reverse transcription, RNA can be used as a template to produce
DNA, but an understanding of the central hypothesis that genetic information flows from DNA to RNA to
protein is critical to an understanding of biological function. Prior to Watson and Crick’s discovery there
were some in the scientific community that thought proteins might be the repository of genetic
information but no credible evidence has turned up to support this idea. Some recent research has
shown that a high percentage of DNA is transcribed, but not necessarily for proteins. If these genes are
coding for something other than proteins, and what they are coding for, is still open to debate, but this
is an area of research that is probably beyond the scope of a high school biology class.
For students to understand the central dogma they need to have an understanding of the
structure of DNA at the levels of nucleotides, genes and chromosomes and an understanding of the
structures of the different forms of RNA. The “Tour of the Basics” website will give them a visual and
auditory introduction to the basic terminology of molecular genetics and an overview of the processes
of replication, transcription and translation.
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ADVANCE PREPARATION:
Though Biology curricular sequencing may vary from district to district, from school to school
and from teacher to teacher, it is assumed for the purposes of this lesson that students will have already
been introduced to the four basic macromolecules, cellular structure and function, cell reproduction and
Mendelian genetics. The material in this lesson will review and extend those concepts. A brief lecture
on the idea of the central dogma preceding the lesson might be beneficial but the intent of this lesson is
to introduce the students to the terminology they need to better understand the broader concepts.
1. Arrange for sufficient internet access
2. (Optional) make arrangements for screen projection of powerpoints and/or animations.
3. Make copies of “Tour of the Basics” comprehension worksheet.
PROCEDURE:
1. Initiate a class discussion about how it is that students seem to be a blend of the traits in their
two parents and how their siblings are a different blend of these traits to introduce the idea of
heredity.
(5 minutes)
2. Give a brief lecture/overview of the idea of the central dogma of biology. At this point limit the
content to DNA to RNA to protein and where this happens. This could be done with whiteboard
or chalkboard, or if screen projection from computer is available, with powerpoints or
animations. Suggestions for animations can be found in references/resources below. (5
minutes).
3. Distribute “Tour of the Basics” comprehension worksheet and instruct students to access the
internet and navigate to the URL address given at the top of the worksheet. Explain the use of
the navigation tools at the top and bottom of that website to answer the comprehension
questions. (35 - 50 minutes).
ASSESSMENT SUGGESTIONS: Check worksheet for completion and comprehension.
REFERENCES AND RESOURCES:
1. ^ Crick, F.H.C. (1958): On Protein Synthesis. Symp. Soc. Exp. Biol. XII, 139-163. (pdf, early draft of
original article)
2. ^ a b Crick, F (August 1970). "Central dogma of molecular biology.". Nature 227 (5258): 561–3.
Bibcode:1970Natur.227..561C. doi:10.1038/227561a0. PMID 4913914.
3. ^ Leavitt, Sarah A.; Marshall Nirenberg (June 2010). "Deciphering the Genetic Code: Marshall
Nirenberg". Office of NIH History.
4. ^ Ahlquist P (May 2002). "RNA-dependent RNA polymerases, viruses, and RNA silencing".
Science 296 (5571): 1270–3. Bibcode:2002Sci...296.1270A. doi:10.1126/science.1069132.
PMID 12016304.
5. ^ B. J. McCarthy and J. J. Holland (September 15, 1965). "Denatured DNA as a Direct Template
for in vitro Protein Synthesis". Proceedings of the National Academy of Sciences of the United
States 54 (3): 880–886. Bibcode:1965PNAS...54..880M. doi:10.1073/pnas.54.3.880.
PMC 219759. PMID 4955657.
6. ^ .T. Uzawa, A. Yamagishi, T. Oshima (2002-04-09). "Polypeptide Synthesis Directed by DNA as a
Messenger in Cell-Free Polypeptide Synthesis by Extreme Thermophiles, Thermus thermophilus
HB27 and Sulfolobus tokodaii Strain 7". The Journal of Biochemistry 131 (6): 849–853.
PMID 12038981.^ Wilkins, Adam S. (January 2012). "(Review) Evolution: A View from the 21st
Century". Genome Biology and Evolution. doi:10.1093/gbe/evs008.
16
7. ^ Moran, Laurence A (May–June 2011). "(Review) Evolution: A View from the 21st Century".
Reports of the National Center for Science Education 32.3 (9): 1–4.
8. ^ Horace Freeland Judson (1996). "Chapter 6: My mind was, that a dogma was an idea for which
there was no reasonable evidence. You see?!". The Eighth Day of Creation: Makers of the
Revolution in Biology (25th anniversary edition). Cold Spring Harbor, NY: Cold Spring Harbor
Laboratory Press. ISBN 0-87969-477-7.
9. ^ a b
http://www.nature.com/nature/journal/v496/n7446/full/496419a.html?WT.ec_id=NATURE20130425
17
Name ____________________
Period ________
Tour of the Basics Comprehension Worksheet
Instructions: Type in the following URL address and use the navigation tools at the top and bottom of the screen to
answer the following comprehension questions with the appropriate word(s), phrase or sentence:
http://learn.genetics.utah.edu/content/begin/tour/
DNA
What is the shape of DNA?
What does “DNA” stand for?
What four letters symbolize the genetic code that is found in the interior of a
DNA molecule?
What do these four letters stand for?
Gene
What is a gene?
Approximately how many genes do we find in a human?
Hemoglobin is a protein that is coded for by a few genes. What does it do?
What do we call it when there is a change in a gene?
Chromosome What is a chromosome?
How many chromosomes do we find in most human cells?
Which pair of chromosomes determines our sex?
Protein
What is a protein?
What relationship do genes have to proteins?
Where in a cell does transcription occur?
18
What organelle is the site of translation?
Heredity
What is heredity?
How many chromosomes do we receive from each parent?
What is the name of the cell that results from a sperm cell fertilizing an egg?
Explain how each human born is genetically unique?
Trait
What is a trait?
Name three types of traits.
What, besides our genes, determines our traits?
What is an allele?
In a heterozygous condition which allele will be expressed?
What percentage of our DNA do all humans share?
19
Name _____________________
Period ________
Tour of the Basics Comprehension Worksheet
Answer Key
Instructions: Type in the following URL address and use the navigation tools at the top and bottom of
the screen to answer the following comprehension questions with the appropriate word(s), phrase or
sentence:
http://learn.genetics.utah.edu/content/begin/tour/
DNA
What is the shape of DNA? Double helix
What does “DNA” stand for? Deoxyribonucleic Acid
What four letters symbolize the genetic code that is found in the interior of a DNA
molecule? A, T, C, G
What do these four letters stand for?
Adenine, Thymine, Cytosine, Guanine
Gene
What is a gene? Genes are instruction manuals for our bodies. They are directions
for all the proteins that make our bodies function
Approximately how many genes do we find in a human? 25,000
Hemoglobin is a protein that is coded for by a few genes. What does it do?
It’s a part of our blood that captures and carries oxygen.
What do we call it when there is a change in a gene? A mutation.
Chromosome What is a chromosome? They are efficient storage units for DNA wrapped tightly
around some proteins.
How many chromosomes do we find in most human cells? 46
Which pair of chromosomes determine our sex? The X and Y chromosomes
Protein
What is a protein? Proteins are the tiny machines that make all living things
function, much like the different parts of a car make it function.
What relationship do genes have to proteins? Each gene in the DNA encodes
information about how to make an individual protein.
Where in a cell does transcription occur? In the nucleus.
20
What organelle is the site of translation? A ribosome
Heredity
What is heredity? The passing of traits from parent to child.
How many chromosomes do we receive from each parent? 23
What is the name of the cell that results from a sperm cell fertilizing an egg?
A zygote
Explain how each human born is genetically unique?
Since the parents contribute chromosomes randomly to each new child, every child
inherits a unique set of chromosomes.
Trait
What is a trait? A trait is a notable feature or quality in a person. Each of us has a
different combination of traits that makes us unique.
Name three types of traits.
1. Physical traits
2. Behavioral traits
3. Predisposition to medical conditions.
What, besides our genes, determines our traits?
The non-genetic, or “environmental”, influences in our lives are just as important
in shaping our traits as the instructions encoded in our genes.
What is an allele? An allele is a set of instructions for each form of a particular
trait.
In a heterozygous condition which allele will be expressed?
The dominant allele will be expressed.
What percentage of our DNA do all humans share? 99.9%
21
Lesson #3 – Diagnosing Diabetes
KEY QUESTIONS: How does the human body maintain homeostasis with respect to blood sugar levels?
What is the role of hormones and other proteins in both the healthy and diseased state?
SCIENCE CONCEPTS: diabetes, genetics, mutation, hormones, homeostasis, regulation, enzymatic
function
OVERALL TIME ESTIMATE: Two 40 minute class periods plus homework. Part one may be done as prelab homework.
LEARNING STYLES: Visual, Auditory and Kinesthetic
VOCABULARY:
Blood plasma – the liquid component of blood. In humans approximately 1% of it consists of a variety
of solutes such as glucose, hormones, salts and the like
Diabetes - group of similar disease states that in one way or another disrupt the body’s ability to
maintain homeostasis with respect to blood sugar levels. The two main forms would be:
Type 1 diabetes, wherein the pancreas fails to produce insulin, and
Type 2 diabetes, wherein there is a failure of the receptor proteins on multiple cell
surfaces that prevent insulin from promoting the uptake of glucose.
Enzyme – a protein that serves as an organic catalyst, i.e., it promotes biochemical reactions without
being consumed in them by lowering the activation energy required to make them go forward. Their
shape is critical to their function as there is an active site on them that conforms to the shape of the
substrate (reactants)
Feedback Control Mechanisms - process in which the level of one substance influences the level of
another substance
Genetics - the study of heredity and the variation of inherited characteristics
Glucose - A monosaccharide sugar, C6H12O6, occurring widely in most plant and animal tissue. It is the
principal circulating sugar in the blood and the major energy source of the body.
Homeostasis - the tendency of a system, especially the physiological system of higher animals, to
maintain internal stability, owing to the coordinated response of its parts to any situation or stimulus
that would tend to disturb its normal condition or function
Hormone - any of various internally secreted compounds, as insulin or thyroxine, formed in endocrine
glands that affect the functions of specifically receptive organs or tissues when transported to them by
the body fluids
Insulin - a polypeptide hormone, produced by the beta cells of the islets of Langerhans of the pancreas,
which regulates the metabolism of glucose and other nutrients.
Receptors – a molecule usually found on the surface of a cell that receives chemical signals from outside
the cell
Regulation – the process of turning genes on and off
LESSON SUMMARY: Students sequence graphically presented information about the maintenance of
blood sugar homeostasis in both the healthy and diabetic person. Students analyze simulated blood
plasma samples collected during a glucose tolerance test for diabetes. They test glucose and insulin
levels to determine if the patient has Type 1 or Type 2 diabetes.
22
STUDENT LEARNING OBJECTIVES: Students should be able to:
1) Sequence graphic information about the causes, symptoms and treatments of maintenance of
blood sugar homeostasis in the healthy and diabetic condition
2) Test and graph the glucose levels in simulated blood plasma samples collected during the
fictional patient’s glucose tolerance test.
3) Test and graph the insulin levels in simulated blood plasma samples collected during the
fictional patient’s glucose tolerance test.
4) Analyze the test results to determine if the patient has Type 1 or Type 2 diabetes.
STANDARDS:
SC.912.N.1.1 Define a problem based on a specific body of knowledge, for example:
biology, chemistry, physics, and earth/space science, and do the following:
1. pose questions about the natural world,
2. conduct systematic observations,
3. examine books and other sources of information to see what is already known,
4. review what is known in light of empirical evidence,
5. plan investigations,
6. use tools to gather, analyze, and interpret data (this includes the use of measurement in metric and
other systems, and also the generation and interpretation of graphical representations of data, including
data tables
and graphs),
7. pose answers, explanations, or descriptions of events,
8. generate explanations that explicate or describe natural phenomena (inferences),
9. use appropriate evidence and reasoning to justify these explanations to others,
SC.912.L.14.6 Explain the significance of genetic factors, environmental factors, and
pathogenic agents to health from the perspectives of both individual and public health.
S.C.912.L.14.29 Define the terms endocrine and exocrine
S.C.912.L.14.30 Compare endocrine and neural controls of physiology
S.C.912.L.14.31 Describe the physiology of hormones including the different types and the mechanisms
of their actions.
S.C.912.L.14.46 Describe the physiology of the the digestive system, including mechanical digestion,
chemical digestion, absorption and the neural and hormonal mechanisms of control.
23
MATERIALS:
Science Take-Out Kit STO-117 “Diagnosing Diabetes” (see Advance Preparation section) which includes:
• 5 tubes of simulated “Blood Plasma” (0, 30, 60, 90 and 120 minutes)*
• 1 tube of simulated “Insulin Indicator” **
• 6 labeled droppers
• Simulated “Glucose Test Paper”***
• Glucose/Insulin Test Color Charts
• Glucose Tolerance Testing Sheet
• Colored sheet of graphics for What You Should Know About Diabetes and the Glucose Tolerance Test
Teacher provided supplies:
Safety goggles
Paper towels for clean up
Scissors
Tape or glue
*simulated Blood Plasma is actually:
Product Ingredients - % Weight/Volume (balance is water)
pH 3 buffer Sulphamic acid (0.10%), Potassium biphthalate (0.35%)
pH 7 buffer Potassium phosphate monobasic (0.15%), Sodium phosphate dibasic (0.30%)
pH 9 buffer Sodium carbonate (0.10%), Sodium bicarbonate (0.35%)
** Simulated Insulin Indicator is actually:
Methyl Red (0.05%), Bromothymol Blue Sodium Salt (0.05%), Water (99.9%
***Glucose Test Paper is actually:
Hydrion pH paper strips scale 1 to 12
BACKGROUND INFORMATION:
Diabetes is not a single disease, but rather a group of similar disease states that in one way or
another disrupt the body’s ability to maintain homeostasis with respect to blood sugar levels. In a
healthy (i.e, non-diabetic) person a high level of glucose in the blood stream due to intake and digestion
of carbohydrates would stimulate beta cells in structures called the islets of Langerhans located in the
pancreas to release the hormone insulin into the blood stream. Insulin is a protein that travels
throughout the body via the blood stream and encounters other receptor proteins on the surface of
liver and muscle cells. Those receptor proteins in turn stimulate the intake of glucose into those cells so
it can be stored as the complex carbohydrate glycogen in the liver (anabolic reactions) or directly utilized
by muscle cells to drive cellular activities. In the opposite scenario, that is, when glucose levels in the
blood stream fall below a set level, the pancreas responds by producing another hormone called
glucagon which stimulates the liver to initiate catabolic breakdown of glycogen back into glucose and rerelease into the blood stream. If these processes are disrupted by diabetes the initial symptoms may
include frequent urination, increased thirst, increased hunger, blurred vision and a number of skin
rashes. More acute symptoms might include diabetic ketoacidosis (which makes the breath smell of
acetone), hyperventilation, nausea, vomiting, abdominal pain and altered states of consciousness (up to
and including coma). Long term complications are mostly related to damage to blood vessels in various
24
tissues and organs throughout the body and might include increased risk of cardiovascular disease,
blindness, nerve damage and chronic kidney disease.
There are many forms of diabetes, but most cases fall into two categories, Type 1 diabetes
mellitus and Type 2 diabetes mellitus. In Type 1, which accounts for about 10% of U.S. cases, pancreatic
production of insulin declines to essentially zero so there is no check on blood sugar levels. Despite a
great deal of research the reasons for this are incompletely understood. Much of the research points
toward it being an autoimmune response, i.e, so-called autoantibodies develop in response to some
environmental trigger and they in turn induce the development of activated T cells capable of destroying
the insulin producing beta cells. Over time secretion of insulin declines to a point where 80 to 90% of
the beta cells are destroyed and the symptoms start to become apparent. Recent research has shown
that another protein with the rather ironic acronym IHoP (Islet Homeostasis Protein), which is not
expressed in the post-diabetic state, may play a role in maintaining the ability of the pancreatic islet cells
to produce insulin. In Type 2, which accounts for about 90% of U.S. cases, the ability of the pancreas to
produce insulin is not compromised, but the aforementioned receptor proteins on the surface of liver
and other cells do not respond to insulin and thus the blood glucose levels can remain dangerously high.
At present neither Type 1 nor Type 2 is curable, but both are treatable. Type 1 treatment includes
regulation of diet and exercise, strict life-long monitoring of blood sugar levels and administration of
exogenous insulin. Type 2 treatment also involves regulation of diet and exercise, monitoring of blood
sugar, oral medications to increase insulin uptake and sometimes administration of exogenous insulin.
Insulin is a fairly small protein consisting of only 51 amino acids in two chains linked together
with disulfide bonds. Its biochemical nature is fairly consistent in mammals and it was first extracted
from dog pancreatic tissue in the 1920’s by Frederick Banting and J.R.R. Macleod at the University of
Toronto. Shortly thereafter they found that it could be more easily extracted from fetal bovine
pancreas. They injected it in children in diabetic comas who prior to that treatment would have been
considered terminal and for the next half century that became the standard source of exogenous insulin
for diabetic patients. Bovine insulin certainly saved many lives but it is not an exact match to human
insulin and so presented immunological problems for some patients. The amino acid structure of insulin
was characterized by Frederick Sanger in the early 1950’s and synthetic insulin was first produced in the
early 1960’s. When the field of recombinant DNA technology began to heat up in the 1970’s scientists
at Genentech collaborated to produce the first genetically engineered human insulin which became
commercially available in 1982. Today nearly all human insulin is mass-produced by introducing the
human gene for insulin into either E.coli bacteria or yeast (Saccharomyces cerevisiae) cultures. The fact
that this can be done and is such an important part of the lives of so many people makes it a good
linkage to showing students the universality of DNA and the validity of inquiry in to molecular genetics.
25
ADVANCE PREPARATION:
As noted above some of the materials for Diagnosing Diabetes should be readily available in any
reasonably equipped high school science department. The kit itself and the accompanying supplies,
background information, question sheets, directions and graphics are available from the Life Sciences
Learning Center at the University of Rochester. The contact information for them is:
Science Take-Out
P.O. Box 205
Pittsford, NY 14534
(585)764-5400 phone
(585)381-9495 fax
[email protected]
A pdf version of Diagnosing Diabetes can be found at the following URL:
http://www.shop.sciencetakeout.com/products.php?id=32
Depending on curricular sequence, molecular genetics should fall far enough into the academic year that
some sample kits could be obtained well in advance of the actual need for them. By doing this at the
beginning of the school year decisions could be made about how many kits need to be obtained for the
actual lab and how much of the material can be formulated from supplies on hand. At minimum the pdf
version should be accessed, downloaded, read and fully considered well in advance of attempting the
lab. If cost is not a consideration and the intent is just to obtain, use and discard the materials from
Science Takeout then the following advice can be ignored, but if the intent is to reuse the graphics it
would be wise to follow one particular optional direction in the kit under the heading “Teacher
preparation”. That would be to laminate the “Graphics for what you should know about Diabetes and
the Glucose Tolerance Test” sheets.
PROCEDURES:
1. Using the pre-test questions on diabetes as a starting point, initiate a class discussion on prior
knowledge of diabetes. (5 – 10 minutes).
2. Using the background information above and references and resources below give a brief
overview of the molecular basis of blood glucose homeostasis and its relationship to diabetes. (5
– 10 minutes)
3. Carry out Part 1 of the Diagnosing Diabetes protocol involving the sequencing of diabetes
related knowledge. While the Science Takeout instructions suggest that this could be done as a
pre-procedure homework assignment it would probably save on paper to just do this in class.
(20 – 30 minutes)
4. Carry out Part 2 of Diagnosing Diabetes - Analyzing Blood Glucose Levels (40 minutes)
5. Carry out Part 3 of Diagnosing Diabetes – Analyzing Blood Insulin Levels (40 minutes)
The length of your class periods will, of course, determine how you divide up the procedures.
26
ASSESSMENT SUGGESTIONS:
Students can be assessed on their successful sequencing of graphical information and
completion of comprehension questions in Part 1; plotting and interpretation of data in Part 2; and
plotting and interpretation of data in Part 3 of the Diagnosing Diabetes laboratory.
REFERENCES AND RESOURCES:
Diagnosing Diabetes is available from Science Takeout (see contact information in Advance Preparation
above).
STUDENT PAGES: Accessible in Diagnosing Diabetes pdf:
http://prod.cpet.ufl.edu/wp-content/uploads/2013/10/Diabetes-with-student-pages.pdf
TEACHER PAGES: Accessible in Diagnosing Diabetes pdf:
http://prod.cpet.ufl.edu/wp-content/uploads/2013/10/Diabetes-with-student-pages.pdf
1. ^ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006.
2. ^ a b c d Shoback, edited by David G. Gardner, Dolores (2011). Greenspan's basic & clinical
endocrinology (9th ed.). New York: McGraw-Hill Medical. pp. Chapter 17. ISBN 0-07-162243-8.
3. ^ a b Williams textbook of endocrinology (12th ed.). Philadelphia: Elsevier/Saunders. pp. 1371–
1435. ISBN 978-1-4377-0324-5.
4. ^ Lambert, P.; Bingley, P. J. (2002). "What is Type 1 Diabetes?". Medicine 30: 1–5.
doi:10.1383/medc.30.1.1.28264. Diabetes Symptoms edit
5. ^ Rother KI (April 2007). "Diabetes treatment—bridging the divide". The New England Journal of
Medicine 356 (15): 1499–501. doi:10.1056/NEJMp078030. PMID 17429082.
6. ^ a b "Diabetes Mellitus (DM): Diabetes Mellitus and Disorders of Carbohydrate Metabolism:
Merck Manual Professional". Merck Publishing. April 2010. Retrieved 2010-07-30.
7. ^ Dorner M, Pinget M, Brogard JM (May 1977). "Essential labile diabetes". MMW Munch Med
Wochenschr (in German) 119 (19): 671–4. PMID 406527.
8. ^ Lawrence JM, Contreras R, Chen W, Sacks DA (May 2008). "Trends in the prevalence of
preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse
population of pregnant women, 1999–2005". Diabetes Care 31 (5): 899–904. doi:10.2337/dc072345. PMID 18223030.
9. ^ Handelsman Y, MD. "A Doctor's Diagnosis: Prediabetes". Power of Prevention 1 (2).
10. ^ a b "Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications" (PDF).
World Health Organisation. 1999.
11. ^Atkinson, M.A. “The Pathogenesis and Natural History of Type 1 Diabetes”. Cold Spring Harbor
Perspectives in Medicine 2012;2:a007641.
12. Herold, K.C., Vignali, D.A.A., Cooke, A., Bluestone, J.A., (April 2013). “Type 1 diabetes: translating
mechanistic observations into effective clinical outcomes”. Nature Reviews/Immunology. 13:
243-256
13. Oh, Seh-Hoon, Darwiche, H, Cho, J, Shupe, T., Petersen, B.E. “Characterization of a novel
functional protein in the pancreatic islet: IhoP regulation of glucagon synthesis in alpha-cells”
Pancreas. 2012 January ; 41 (1): 22-30
27
LESSON #4 – Diabetes and the Central Dogma (PowerPoint)
KEY QUESTIONS: How is genetic information stored, transcribed and translated into functional proteins
in humans and other living organisms? What is the relationship between an organism’s ability to make
specific proteins and its ability to maintain homeostasis?
SCIENCE CONCEPTS: DNA, genetic expression, mutation, regulation, replication, RNA, transcription,
translation
OVERALL TIME ESTIMATE: 60 - 80 minutes
LEARNING STYLES: Visual and auditory.
VOCABULARY:
Ambiguity –the idea in reference to the genetic code that a particular codon might code for more than
one amino acid. This is not true of the genetic code, i.e., there is no ambiguity.
Amino acid – one of twenty monomers of proteins. Each of them have a central carbon atom
surrounded by an amine group, a carboxyl group, a hydrogen atom and a side group (referred to as the
“R-group” that is unique to each one.
Anti-codon – a group of three nitrogen bases found at one end of a transfer RNA that would be
complementary to a codon found on a messenger RNA
Central Dogma – more properly called a hypothesis, rather than a dogma, but it refers to the flow of
genetic information from DNA to RNA to proteins
Codon – a group of three nitrogen bases found in sequences of messenger RNA that code for a specific
amino acid
Complementary Base Pairing – an attraction between pairs of nitrogen bases found in nucleic acids
based on easily broken hydrogen bonds. Two of the five bases found in nucleic acids, adenine and
guanine are purines and they respectively bond with thymine and cytosine which are pyrimidines. In
RNA thymine is replaced by uracil, another pyrimidine
DNA – deoxyribonucleic acid, a molecule which is the main repository of genetic information in most
living organisms. It is a double-stranded polymer which assumes a helical shape and consists of
monomers of nucleotides which in turn consist of one deoxyribose sugar, one phosphate and one of
four nitrogen bases, adenine, guanine, cytosine and thymine
Degeneracy – the phenomenon that the genetic code is redundant, i.e., a given amino acid can be coded
for by more than one codon
Deletion – a form of genetic mutation wherein a nitrogen base is removed or left out thus leading to a
frame shift, i.e., the manner in which a sequence is read
Diabetes - group of similar disease states that in one way or another disrupt the body’s ability to
maintain homeostasis with respect to blood sugar levels. The two main forms would be:
Type 1 diabetes, wherein the pancreas fails to produce insulin, and
Type 2 diabetes, wherein there is a failure of the receptor proteins on multiple cell
surfaces that prevent insulin from promoting the uptake of glucose.
Double Helix – the shape of a DNA molecule as postulated by Watson and Crick. It is like a twisted
ladder wherein the sides are constructed of alternating sugars and phosphates and the rungs of nitrogen
bases held weakly together by nitrogen bonds.
Enzyme – a protein that serves as an organic catalyst, i.e., it promotes biochemical reactions without
being consumed in them by lowering the activation energy required to make them go forward. Their
28
shape is critical to their function as there is an active site on them that conforms to the shape of the
substrate (reactants)
Exon – that part of a primary mRNA transcript that will actually serve as a source of coding to construct
the protein
Frame shift Mutation – a change in a gene sequence consisting of either an insertion or a deletion of a
nucleotide that from that point forward changes the manner in which the sequence will be transcribed
or translated
Gene – a sequence of nucleotides along one side of a DNA molecule that contains coded information for
a specific polypeptide
Glucose - A monosaccharide sugar, C6H12O6, occurring widely in most plant and animal tissue. It is the
principal circulating sugar in the blood and the major energy source of the body.
Homeostasis - the tendency of a system, especially the physiological system of higher animals, to
maintain internal stability, owing to the coordinated response of its parts to any situation or stimulus
that would tend to disturb its normal condition or function
Insertion – a form of genetic mutation wherein a nucleotide is added to an existing sequence thus
leading to a frame shift, i.e., a change in the manner the sequence is transcribed or translated
Intron – a non-coding sequence within a primary mRNA transcript
Mutation – a change in a gene sequence
Nucleotide – a monomer of the polymers DNA or RNA consisting of one sugar, one phosphate and one
of the nitrogen bases adenine, thymine, guanine, cytosine or uracil
Point Mutation – a change in a gene sequence of a single nucleotide
Polymer – a molecule consisting of a series of repeating similar units, or monomers. Examples would be
complex carbohydrates, proteins and nucleic acids
Polypeptide – a long, continuous and unbranched chain of amino acids held together by peptide bonds
Protein - large biological molecules consisting of one or more chains of amino acids that perform a vast
array of functions within living organisms
Protein Structure - the biomolecular structure of a protein molecule. Each protein is a polymer –
specifically a polypeptide – that is a sequence formed from various L-α-amino acids
Replication – the process of producing two identical DNA copies from one original DNA molecule
Transcription - the first step of gene expression, in which a particular segment of DNA is copied into RNA
by the enzyme, RNA polymerase
Translation - is the process in which cellular ribosomes create proteins. It is part of the process of gene
expression
LESSON SUMMARY: This lesson is a straightforward exercise in transmitting content via powerpoint
while students take notes and are encouraged to ask questions based on the text and images they are
seeing.
STUDENT LEARNING OBJECTIVE: Students should be able to:
1. Define the basic terminology of heredity at the organismic, cellular and molecular levels
2. Sequence the steps of the central dogma of biology
3. Explain the relationship between homeostasis and protein production
29
STANDARDS:
SC.912.L.14.6 Explain the significance of genetic factors, environmental factors, and
pathogenic agents to health from the perspectives of both individual and public health.
S.C.912.L.14.29 Define the terms endocrine and exocrine
S.C.912.L.14.30 Compare endocrine and neural controls of physiology
S.C.912.L.14.31 Describe the physiology of hormones including the different types and the mechanisms
of their actions.
S.C.912.L.14.46 Describe the physiology of the the digestive system, including mechanical digestion,
chemical digestion, absorption and the neural and hormonal mechanisms of control.
SC.912.L.14.52 Explain the basic functions of the human immune system, including specific
and nonspecific immune response, vaccines, and antibiotics.
SC.912.L.16.3 Describe the basic process of DNA replication and how it relates to the transmission and
conservation of the genetic information
SC.912.L.16.4 Explain how mutations in the DNA sequence may or may not result in phenotypic change.
Explain how mutations in gametes may result in phenotypic changes in offspring.
S.C.912.L.16.5 Explain the basic processes of transcription and translation, and how they result in the
expression of genes.
S.C.912.L.16.6 Discuss the mechanisms for regulation of gene expression in prokaryotes and eukaryotes
at transcription and translation level
SC.912.L.18.1 Describe the basic molecular structures and primary functions of the four major categories
of biological macromolecules.
SC.912.L.18.4 Describe the structures of proteins and amino acids. Explain the functions of proteins in
living organisms. Identify some reactions that amino acids undergo. Relate the structure and function of
enzymes.
MATERIALS:
Computer
Projection equipment
30
BACKGROUND INFORMATION:
The central dogma of biology is an explanation of how genetic information is stored, transcribed
and translated into functional proteins in living organisms. A basic understanding of its tenets is critical
to making sense of genetics and molecular biology, and, by extension, physiology, medicine, and many
other aspects of biology currently at the forefront of the living sciences. Given that most of the
processes involved are occurring at a scale below that perceivable by light, and in some cases, electron
microscopy, the teaching of it relies heavily on the student’s ability to understand concepts they can
only visualize indirectly.
DNA (Deoxyribonucleic acid) was shown by James Watson and Francis Crick to be a molecule
that assumes a double helix (twisted ladder) shape. The sides of the ladder are composed of alternating
deoxyribose sugars and phosphates. The rungs of the ladder are, however, the repository of genetic
information that directs the production of proteins in both prokaryotic and eukaryotic cells. That
information is contained in the sequence of four nitrogen bases, adenine, thymine, guanine and cytosine
which are often symbolized as A, T, G, and C. Adenine is weakly attracted by hydrogen bonds to
thymine and similarly guanine is attracted to cytosine in a phenomenon known as complementary base
pairing. The genetic information is in the form of triplets of nitrogen bases that ultimately code for
amino acids, the building blocks of proteins. Because of complementary base pairing each side of a DNA
molecule can serve as a template for reliable replication of this genetic information as an antecedent to
cell division so that each new cell will have a complete set of instructions to make all the proteins
necessary for that particular organism. This replication is accomplished with the aid of several enzymes
that are themselves proteins. Helicase opens up the helix at several locations. Polymerase brings in free
nucleotides, consisting of one sugar, one phosphate and the complementary base. Ligase ties the
nucleotides together.
RNA (Ribonucleic acid) differs from DNA in that it is single stranded, contains the sugar ribose
and ′′contains the nitrogen base uracil in place of thymine; uracil being complementary to adenine in the
way thymine is in DNA. RNA comes in three forms, messenger RNA (mRNA), ribosomal RNA (rRNA) and
transfer RNA (tRNA),all of which are involved in the transfer of information from nuclear DNA to
cytoplasmic organelles for the production of proteins. Recent research has also unearthed some small
endogenous classes of RNA, microRNA (miRNA) and small interfering RNA (siRNA) that regulate the
production of proteins, but their modus operandi is not completely understood at this time. DNA and
mRNA are the molecules directly involved in transcription. This is a process wherein a section of DNA,
known as a gene, that codes for a protein opens up and with the help of the enzyme RNA polymerase
free RNA nucleotides temporarily bind to the appropriate section of DNA. The process is initiated at
sequences of DNA known as promoter regions, continues through the coding region and is terminated
by one of three possible stop codons called terminators. The mRNA then peels away from the DNA and
makes its way through the nuclear pores to a two-part organelle made of rRNA called a ribosome. Some
of these are free in the cytoplasm and some are found on the surface of endoplasmic reticulum.
Before they reach the ribosomes, however, some non-coding parts of the mRNA, called introns, are
excised from the message with the help of enzymes and the coding parts, called exons, are spliced
together. Other enzymes aid in adding a guanine nucleotide cap to the 5′ end and a poly-A (adenine)
cap to the 3′ end to distinguish which end should go in to the ribosome first and to prevent hydrolytic
enzymes from destroying the mRNA before it gets translated.
Once transcription and post-transcriptional processing are completed the mRNA is ready to be
translated at a ribosome. A ribosome is made of two sub-units, a small one and a large one. The small
sub-unit attaches to the 5′ end of the mRNA and a tRNA with the amino acid methionine attached to it.
The small subunit moves along the mRNA until it reaches the start codon AUG whereupon the
complementary anti-codon UAC on the tRNA binds temporarily to the mRNA, the large sub-unit attaches
and the process of translation commences. The ribosome starts moving along the mRNA three bases at
31
a time and tRNAs with anti-codons complementary to the codon being presented at that site and the
appropriate amino acid at the other end of the tRNA are added to a growing polypeptide chain.
Eventually one of three codons, UAA, UAG, or UGA that all signify “Stop”, is reached and the process of
translation is terminated. The mRNA peels away from the ribosome as does the polypeptide. The
sequence of amino acids at this point is referred to as the primary structure. Post-translationally the
side chains of the various amino acids in the polypeptide begin to interact with their aqueous
environment and one another and fold into secondary and tertiary structures and thence into functional
proteins. If another polypeptide is required to interact with the first one to achieve functional status the
combination of the two (or more) of them is referred to as the quaternary structure.
All of this works amazingly efficiently given how frequently it has to occur to maintain the
proper functioning of cells in unicellular organisms and cells, tissues and organs in multicellular
organisms. There is, however, the occasional mutation. It depends on the nature of the mutation as to
whether its effect is negative, positive or moot. If, for instance, a single nitrogen base is replaced with
another one in a point mutation known as a substitution, and it happens to be the third base in the
triplet or codon there is a good chance it will have no effect due to the redundant nature of the genetic
code. If it’s the first or second base in the codon chances are that a different amino acid will be called for
and that can change the structure and therefore function of the resulting protein. If a single base is
removed or added, known respectively as a deletion or an addition, and collectively as frame-shift
mutations, then, as the name implies all of the message after that mutation will be read differently and
most likely the structure and function of the resulting protein will be radically altered. Occasionally
these altered proteins actually work better than the original protein and/or give the organism some
adaptive trait that it didn’t previously possess. This is the basis of evolutionary change.
ADVANCE PREPARATION:
Read through the PowerPoint for comprehension and make editorial changes as desired.
Ensure that embedded links to animations function properly on your system if you choose to use them.
PROCEDURES:
Depending on your individual teaching style this PowerPoint can serve as just a straight dissemination of
content/note-taking exercise or a jumping off point for a dialogue on the concepts depicted.
ASSESSMENT SUGGESTIONS:
Post test
Unit test
Performance on From DNA to Protein Structure and Function lab
Biology EOC
IB, AP, or AICE Biology tests.
REFERENCES AND RESOURCES:
32
Helpful animations:
http://www.dnalc.org/resources/3d/central-dogma.html
http://www.wiley.com/college/boyer/0470003790/animations/central_dogma/central_dogma.swf
http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter3/animation__mrna_synthesis__transcription___qui
z_1_.html
http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter3/animation__how_translation_works.html
http://naturedocumentaries.org/2149/central-dogma-biology-2008/
http://www.wisc-online.com/objects/ViewObject.aspx?ID=AP1302
1. ^ Crick, F.H.C. (1958): On Protein Synthesis. Symp. Soc. Exp. Biol. XII, 139-163. (pdf, early draft of
original article)
2. ^ a b Crick, F (August 1970). "Central dogma of molecular biology.". Nature 227 (5258): 561–3.
Bibcode:1970Natur.227..561C. doi:10.1038/227561a0. PMID 4913914.
3. ^ Leavitt, Sarah A.; Marshall Nirenberg (June 2010). "Deciphering the Genetic Code: Marshall
Nirenberg". Office of NIH History.
4. ^ Ahlquist P (May 2002). "RNA-dependent RNA polymerases, viruses, and RNA silencing".
Science 296 (5571): 1270–3. Bibcode:2002Sci...296.1270A. doi:10.1126/science.1069132.
PMID 12016304.
5. ^ B. J. McCarthy and J. J. Holland (September 15, 1965). "Denatured DNA as a Direct Template
for in vitro Protein Synthesis". Proceedings of the National Academy of Sciences of the United
States 54 (3): 880–886. Bibcode:1965PNAS...54..880M. doi:10.1073/pnas.54.3.880.
PMC 219759. PMID 4955657.
6. ^ .T. Uzawa, A. Yamagishi, T. Oshima (2002-04-09). "Polypeptide Synthesis Directed by DNA as a
Messenger in Cell-Free Polypeptide Synthesis by Extreme Thermophiles, Thermus thermophilus
HB27 and Sulfolobus tokodaii Strain 7". The Journal of Biochemistry 131 (6): 849–853.
PMID 12038981.
7. ^ Wilkins, Adam S. (January 2012). "(Review) Evolution: A View from the 21st Century". Genome
Biology and Evolution. doi:10.1093/gbe/evs008.
8. ^ Moran, Laurence A (May–June 2011). "(Review) Evolution: A View from the 21st Century".
Reports of the National Center for Science Education 32.3 (9): 1–4.
9. ^ Horace Freeland Judson (1996). "Chapter 6: My mind was, that a dogma was an idea for which
there was no reasonable evidence. You see?!". The Eighth Day of Creation: Makers of the
Revolution in Biology (25th anniversary edition). Cold Spring Harbor, NY: Cold Spring Harbor
Laboratory Press. ISBN 0-87969-477-7.
10. ^ a b
http://www.nature.com/nature/journal/v496/n7446/full/496419a.html?WT.ec_id=NATURE20130425
STUDENT PAGES: N/A
33
TEACHER PAGES: see attached powerpoint “Diabetes and the Central Dogma” and screen shots below:
34
35
36
37
38
39
LESSON #5 - From DNA to Protein: Structure and Function
KEY QUESTIONS: How is genetic information stored in DNA and how is it used to direct the synthesis of
the many different kinds of proteins that each cell requires? How is the shape of a specific protein
determined? What relationship does the shape of a protein have to its function?
SCIENCE CONCEPTS: central dogma, complementary base pairing, DNA, genetic expression, mutation,
protein function, protein synthesis, RNA, transcription, translation
OVERALL TIME ESTIMATE: Two 40 minute class periods plus homework
LEARNING STYLES: Visual, auditory, and kinesthetic
VOCABULARY:
Amino acid – one of twenty monomers of proteins. Each of them have a central carbon atom
surrounded by an amine group, a carboxyl group, a hydrogen atom and a side group (referred to as the
“R-group” that is unique to each one.
Complementary Base Pairing – an attraction between pairs of nitrogen bases found in nucleic acids
based on easily broken hydrogen bonds. Two of the five bases found in nucleic acids, adenine and
guanine are purines and they respectively bond with thymine and cytosine which are pyrimidines. In
RNA thymine is replaced by uracil, another pyrimidine
DNA – deoxyribonucleic acid, a molecule which is the main repository of genetic information in most
living organisms. It is a double-stranded polymer which assumes a helical shape and consists of
monomers of nucleotides which in turn consist of one deoxyribose sugar, one phosphate and one of
four nitrogen bases, adenine, guanine, cytosine and thymine
Gene – a sequence of nucleotides along one side of a DNA molecule that contains coded information for
a specific polypeptide
Hydrophilic – having an affinity for water
Hydrophobic – having a repulsion to water
Mutation – a change in a gene sequence
Nitrogen Base – nitrogen containing organic molecules found within the nucleic acids DNA and RNA that
have a weak affinity for one another and thus allow for complementary base pairing
Nucleotide – a monomer of the polymers DNA or RNA consisting of one sugar, one phosphate and one
of the nitrogen bases adenine, thymine, guanine, cytosine or uracil
Polypeptide – a long, continuous and unbranched chain of amino acids held together by peptide bonds
Protein - large biological molecules consisting of one or more chains of amino acids that perform a vast
array of functions within living organisms
Transcription - the first step of gene expression, in which a particular segment of DNA is copied into RNA
by the enzyme, RNA polymerase
Translation - is the process in which cellular ribosomes create proteins. It is part of the process of gene
expression
LESSON SUMMARY: Students model how information in the DNA base sequence is transcribed and
translated to produce a protein molecule. They model how interaction between amino acids causes a
protein to fold into a three-dimensional shape that enables the protein to perform a specific function.
STUDENT LEARNING OBJECTIVE: Students should be able to:
40
1. Define the basic terminology of protein expression and function.
2. Sequence the steps of the central dogma of biology.
3. Explain the relationship between structure and function in proteins.
STANDARDS:
SC.912.L.16.3 Describe the basic process of DNA replication and how it relates to the transmission and
conservation of the genetic information
SC.912.L.16.4 Explain how mutations in the DNA sequence may or may not result in phenotypic change.
Explain how mutations in gametes may result in phenotypic changes in offspring.
S.C.912.L.16.5 Explain the basic processes of transcription and translation, and how the result in the
expression of genes.
S.C.912.L.16.6 Discuss the mechanisms for regulation of gene expression in prokaryotes and eukaryotes
at transcription and translation level
S.C.912.L.16.9 Explain how and why the genetic code is universal and is common to all organisms
SC.912.L.16.10 Evaluate the impact of biotechnology on the individual, society and the
environment, including medical and ethical issues.
SC.912.L.18.1 Describe the basic molecular structures and primary functions of the four major categories
of biological macromolecules.
SC.912.L.18.4 Describe the structures of proteins and amino acids. Explain the functions of proteins in
living organisms. Identify some reactions that amino acids undergo. Relate the structure and function of
enzymes.
MATERIALS:
Science Take-Out Kit STO-106 “From DNA to Protein Structure and Function” (see Advance Preparation
section) which includes:
19 inch chenille stem
Universal genetic code chart
Beads – red, blue, yellow, white
From DNA to Protein Record Sheet
Teacher optionally provides red, blue and yellow colored pencils, markers or crayons.
41
BACKGROUND INFORMATION:
The central dogma of biology is an explanation of the flow of genetic information in living
organisms. The term central dogma is attributed to Francis Crick, one of the co-discoverers of the double
helix shape of DNA, who later acknowledged that his use of the term “dogma” was perhaps unfortunate
in that it implied a rigidity of thinking that would stand in opposition to the scientific method. More
than a half century of myriad lines of research have unequivocally confirmed, however, that information
contained in the nitrogen base sequences of DNA is transcribed on to RNA and then translated into
proteins.
This lesson focuses on the transcription and translation of DNA sequences and the posttranslational interactions between the parts of a polypeptide chain that transform it into a functioning
protein. The so-called genetic information in DNA sequences comes in the form of DNA nitrogen base
triplets. These could consist of any one of 64 (43) possible combinations of the four nitrogen bases, i.e.,
adenine (A) and guanine (G), also known as the purine bases, and thymine (T) and cytosine (C), also
known as the pyrimidine bases. Adenine has an affinity to form a hydrogen bond with thymine and
similarly, guanine bonds with cytosine. This tendency to form complementary base pairs allows for
accurate replication of DNA molecules via the addition of complementary free DNA nucleotides to either
side of an opened double helix structure with the aid of appropriate enzymes. It also allows for the
accurate transcription of DNA sequences into sequences of messenger RNA (mRNA) by the temporary
addition of complementary free RNA nucleotides to one side of one section of the DNA molecule known
as a gene. The triplets of mRNA molecules thus transcribed are known as codons because they later
code for specific amino acids by peeling off of the transcribed DNA sequence, leaving the cell nucleus to
seek out a ribosome and translating their information into a specified chain of amino acids. Each codon
only codes for one amino acid but there are 64 codons and only 20 amino acids so there is more than
one codon that can code for a particular amino acid.
A chain of amino acids in a specific sequence as described above is referred to as a polypeptide
because the amino acids are held together by peptide bonds. Interactions that occur between different
parts of the chain post-translationally are what make the chain a functional protein. All amino acids
have in common an amine group, a carboxyl group and a hydrogen atom extending from 3 of the
possible bonds of a central carbon atom, but the 4th bond, the so-called “R” side chain is different in
each one. Some of these side chains are hydrophobic, some are hydrophilic, some are negatively
charged and some are positively charged. Since they exist in the polar medium water the interactions of
the different side chains with the water and with each other make them contort into the shapes that
give them their specific function. This phenomenon explains why a change in a single nitrogen base
back at the DNA level of information (known as a point mutation) can potentially change the structure
and thus the function of the protein that results.
For students to understand the central dogma they need to have an understanding of the
structure of DNA at the levels of nucleotides, genes and chromosomes, an understanding of the
structures of the different forms of RNA, and an understanding of amino acids, polypeptides and
functional proteins This lab will give them a hands-on means of visually and kinesiologically
demonstrating to themselves how these molecules interact with one another to construct the
thousands of different proteins necessary for complex living processes.
42
ADVANCE PREPARATION:
As noted above some of the materials for From DNA to Protein Structure and Function should be readily
available in any reasonably equipped high school science department. The kit itself and the
accompanying supplies, background information, question sheets, directions and graphics are available
from the Life Sciences Learning Center at the University of Rochester. The contact information for them
is:
Science Take-Out
P.O. Box 205
Pittsford, NY 14534
(585)764-5400 phone
(585)381-9495 fax
[email protected]
A pdf version of Diagnosing Diabetes can be found at the following URL:
http://www.cpet.ufl.edu/wp-content/uploads/2012/10/Structure-to-Function.pdf
Depending on curricular sequence, molecular genetics should fall far enough into the academic year that
some sample kits could be obtained well in advance of the actual need for them. By doing this at the
beginning of the school year decisions could be made about how many kits need to be obtained for the
actual lab and how much of the material can be formulated from supplies on hand. At minimum the pdf
version should be accessed, downloaded, read and fully considered well in advance of attempting the
lab. If cost is not a consideration and the intent is just to obtain, use and discard the materials from
Science Takeout then the following advice can be ignored, but if the intent is to reuse the graphics it
would be wise to laminate the “Universal Genetic Code Charts”
PROCEDURE:
1. Reference the Diabetes to Central Dogma power point notes, the background information
above, and the introductory material from the lab kit itself to conduct a short review of the basic
tenets of the central dogma and the relationship of protein folding to their structure and
function. (5 - 10 minutes)
2. Divide students into lab groups and distribute instructions, Universal Genetic Code Charts,
Record Sheets, chenille stems and beads. I would highly recommend you have shallow
containers to corral the beads and have towels or paper towels on the bench top surface or
the beads will be rolling everywhere except where you want them. (If this lab is being done
with multiple classes these items can be distributed to lab benches before class, otherwise allow
about 5 minutes)
3. The instructions are fairly self-explanatory, but depending on the level of the class you may
need to read through them aloud as a group to clear up any misunderstandings. (5 -10 minutes)
4. Carry out Part A. Modeling Protein Synthesis and Protein Folding (30 – 40 minutes)
5. Carry out Part B. Protein Shape and Function (15 – 20 minutes)
6. Carry out Part C. Sickle Cell Anemia – An Error in Protein Structure and Function (15 – 20
minutes)
43
ASSESSMENT SUGGESTIONS:
 Successful completion and demonstration of comprehension of the questions embedded in the
lab
 Demonstration of comprehension of those questions in the post-test related to this topic.
RESOURCES AND REFERENCES:
From DNA to Protein Structure and Function available from Science Takeout (see contact information in
Advance Preparation above).
Helpful websites:
http://publications.nigms.nih.gov/structlife/chapter1.html
http://publications.nigms.nih.gov/psi/timeline_text.html
REFERENCES
1. ^ Brocchieri L, Karlin S (2005-06-10). "Protein length in eukaryotic and prokaryotic proteomes".
Nucleic Acids Research 33 (10): 3390–3400. doi:10.1093/nar/gki615. PMC 1150220.
PMID 15951512.
2. ^ Pauling L, Corey RB, Branson HR (1951). "The structure of proteins; two hydrogen-bonded
helical configurations of the polypeptide chain". Proc Natl Acad Sci USA 37 (4): 205–211.
doi:10.1073/pnas.37.4.205. PMC 1063337. PMID 14816373.
3. ^ Chiang YS, Gelfand TI, Kister AE, Gelfand IM (2007). "New classification of supersecondary
structures of sandwich-like proteins uncovers strict patterns of strand assemblage.". Proteins. 68
(4): 915–921. doi:10.1002/prot.21473. PMID 17557333.
4. ^ Govindarajan S, Recabarren R, Goldstein RA. (17 September 1999). "Estimating the total
number of protein folds.". Proteins. 35 (4): 408–414. doi:10.1002/(SICI)10970134(19990601)35:4<408::AID-PROT4>3.0.CO;2-A. PMID 10382668.
5. ^ . PMID 23056252. Missing or empty |title= (help)
6. ^ Murzin, A. G.; Brenner, S.; Hubbard, T.; Chothia, C. (1995). "SCOP: A structural classification of
proteins database for the investigation of sequences and structures". Journal of Molecular
Biology 247 (4): 536–540. doi:10.1016/S0022-2836(05)80134-2. PMID 7723011. edit
7. ^ Orengo, C. A.; Michie, A. D.; Jones, S.; Jones, D. T.; Swindells, M. B.; Thornton, J. M. (1997).
"CATH--a hierarchic classification of protein domain structures". Structure (London, England :
1993) 5 (8): 1093–1108. doi:10.1016/S0969-2126(97)00260-8. PMID 9309224. edit
8. ^ Zhang Y (2008). "Progress and challenges in protein structure prediction". Curr Opin Struct Biol
18 (3): 342–348. doi:10.1016/j.sbi.2008.02.004. PMC 2680823. PMID 18436442.
STUDENT PAGES: Accessible in From DNA to Protein Structure and Function pdf:
http://www.cpet.ufl.edu/wp-content/uploads/2012/10/Structure-to-Function.pdf
TEACHER PAGES: Accessible in From DNA to Protein Structure and Function pdf:
http://www.cpet.ufl.edu/wp-content/uploads/2012/10/Structure-to-Function.pdf
44
LESSON #6 – Post-test
TIME ESTIMATE: 30 minutes
Post-test
1. List at least five symptoms of diabetes.
2a. What is the principal organ involved in the development of diabetes?
2b. List 3 organs involved in long-term complications of diabetes.
3. As a member of the U.S. population what are the chances you will develop diabetes in your life
time?
A. 0-10%
B. 20-25%
C. 30-40%
D. 60-70%
4. Are you more likely to get Type 1 Diabetes or Type 2 Diabetes?
5. Compare and contrast Type 1 Diabetes and Type 2 Diabetes
45
6. What, if any, is the relationship between DNA and Diabetes?
7. What, if any, is the relationship between DNA and proteins?
8. List at least 3 functions for proteins.
9. State, in as few words as possible, the central dogma of molecular biology.
10. What is a gene?
11. What is a mutation?
12. Name at least two possible outcomes of a genetic mutation.
46
Pre/Post-test Answer Key
1. List at least 5 symptoms of diabetes.
Frequent urination
Excessive Thirst
Hunger
Blurry Vision
Weight Loss/Gain
Fatigue
Diabetic Ketoacidosis
Hyperventilation
Nausea
Vomiting
2a. What is the principal organ involved in the development of diabetes?
Pancreas
Liver
2b. List 3 organs involved in long-term complications of diabetes.
Kidney
Heart
Blood Vessels
Eyes
Nerves
3. As a member of the U.S. population what are the chances you will develop diabetes in your life
time?
C. 30-40%
4. Are you more likely to get Type 1 Diabetes or Type 2 Diabetes?
Type 2
5. Compare and contrast Type 1 Diabetes and Type 2 Diabetes.
In Type-1, the beta cells in the pancreas (which produce insulin) are destroyed by the individual’s own
immune system, meaning those people produce no insulin.
In Type-2, individuals can produce insulin but the insulin receptors on their cell membranes do not
respond properly to the insulin message (signal)
6. What, if any, is the relationship between DNA and Diabetes?
DNA contains the genetic information to create proteins that function all over the body. Changes in
DNA (mutations) can lead to less functional or non-functional proteins, which leads to diseases such as
Diabetes.
7. What, if any, is the relationship between DNA and proteins?
DNA contains the genetic information to create proteins that function all over the body. Changes in
DNA (mutations) can lead to less functional or non-functional proteins.
47
8. List at least 3 functions for proteins.
Structural
Enzymes
Hormones
Regulators
Movement/Transfer
9. State, in as few words as possible, the central dogma of molecular biology.
DNA  RNA  Protein
10. What is a gene?
A sequence of nucleotides along one side of a DNA molecule that contains coded information for a
specific polypeptide
11. What is a mutation?
A change in the gene sequence
12. Name at least two possible outcomes of a genetic mutation.
No Change
Less functional protein
More functional protein
Non-functional protein
48
Acknowledgements
As the author of this work I would like to express my sincere gratitude to Mary Jo Koroly, Julie
Bokor, Drew Joseph, Houda Darwiche and the entire CPET staff for two consecutive great learning
experiences, last summer at the Emerging Pathogens/ICORE Summer Institute and this summer at the
CPET Research Internship. I believe I have learned more than my head can hold.
I would also like to thank Bryon Petersen and all the members of his laboratory for allowing me
to be a nosy fly on the wall observing a truly remarkable research team.
49
Diabetes and the Central Dogma
What do the two types of diabetes
have in common that involves the
Central Dogma?
Proteins that are missing
Why should you care?
Why should you care?
• Odds of getting diabetes depends on race,
gender and level of education
• If you understand the connection
between diet, exercise & lifestyle you
improve the odds of avoiding diabetes
Central Dogma
DNA
• James Watson & Francis
Crick proposed:
• DNA shape a double
helix
• DNA contains genetic
information
• The term “Central
Dogma”
• DNA → RNA → protein
DNA
• Deoxyribonucleic
acid
• Double helix
(twisted ladder)
• Sides =
deoxyribose sugar
& phosphates
• Rungs = nitrogen
bases (A,T,G,C)
DNA nucleotides
• DNA is a polymer of nucleotides
• Poly = many, mer = unit
• DNA nucleotide = one deoxyribose
sugar, one phosphate & one
nitrogen base
Nitrogen bases – complementary
base pairing
•
•
•
•
•
•
A = Adenine
T = Thymine
G = Guanine
C = Cytosine
A attracted to T
G attracted to C
Complementary Base Pairing
• Insures
accurate
replication of
DNA for cell
division
Complementary Base Pairing
• Insures accurate
transcription of
DNA → RNA
Genetic information
Stored in Nitrogen Base
Sequences
• Nitrogen base triplet
codes for an amino
acid
• Example – TAC codes
for methionine
• The four bases can
be combined 64
different ways into
groups of 3
• 43 = 64
Genetic information
Stored in Nitrogen Base
Sequences
•
•
•
•
DNA base triplet sequences = genes
genes code for sequences of amino acids
Amino acid sequences become proteins
Human genome in our 46 chromosomes
holds about 20,000 genes (a complete set
of instructions)
DNA Replication
• DNA replication must
occur before cells
divide so each new
cell will have a
complete set of
genetic instructions
DNA Replication
(simplified)
DNA Replication
(with enzymes)
DNA Replication
(end result)
• Two strands of original chromosomes
were mirror images of each other
• Complementary base pairing allows each
original strand to serve as template
• Replication produces two perfect copies
consisting of one original strand and one
new strand
Back to the Central Dogma
Transcription
• Noun
• (plural transcriptions)
• The act or process of transcribing.
• Something that has been transcribed, including:
– (music) An adaptation of a composition.
– These frame tale interludes frequently include transcriptions of
Italian folk songs.
– A recorded radio or television programme.
– (linguistics) A representation of speech sounds as phonetic
symbols.
• (genetics) The synthesis of RNA under the
direction of DNA.
Transcription
• Genetic information for proteins is coded
in DNA.
• DNA does not leave the nucleus.
• Proteins are made in the cytoplasm.
• Therefore, DNA information must be
transcribed and carried from the nucleus
to the cytoplasm.
• Messenger RNA (mRNA) does this.
RNA vs. DNA
• RNA
• DNA
• Single
• Double
stranded
stranded
• Ribose sugar • Deoxyribose
sugar
• Uracil
• Thymine
Messenger RNA (mRNA)
• Transcribes genes from DNA in nucleus
• Formed from free RNA nucleotides in the
nucleus
• Uses complementary base pairing and
enzymes to transcribe genes
• Is modified after transcription before
leaving the nucleus
DNA to RNA transcription
Transcription animation
• http://highered.mcgrawhill.com/sites/0072507470/student_view0/
chapter3/animation__mrna_synthesis__tra
nscription___quiz_1_.html
Post – transcription changes
• After the mRNA peels off it is modified before it
leaves the nucleus.
• A guanine cap is added to the 5ˊ end and a poly
A (Adenine) cap is added to the 3ˊ end
• Non-coding parts of the message called introns
are cut out & the coding parts called exons are
spliced together by enzymes.
• The mature mRNA then moves through a
nuclear pore to find a ribosome and be
translated
Post transcription animation
• http://www.execulink.com/~ekimmel/mrna_
flash.htm
Translation
•
•
•
•
trans·la·tion (tr ns-l sh n, tr nz-)
n.
1.
a. The act or process of translating, especially from one language
into another.
• b. The state of being translated.
• 2. A translated version of a text.
• 3. Physics Motion of a body in which every point of the body moves
parallel to and the same distance as every other point of the body.
• 4. Biology The process by which messenger RNA directs
the amino acid sequence of a growing polypeptide
during protein synthesis.
Translation
• The information that was transcribed from
DNA to mRNA was in the language of
nucleotide base triplets which are called
codons in mRNA.
• The codons will be translated into the
language of amino acids
Translation
•
•
Translation occurs in the cytoplasm
It requires two other forms of RNA in addition
to mRNA:
rRNA (ribosomal RNA)
tRNA (transfer RNA)
rRNA & tRNA
Ribosomes (rRNA)
Made of small sub-unit
& large sub-unit
Free or on endoplasmic
reticulum
Transfer RNA (tRNA)
Have anti-codon
complementary to
codons at one end
Amino acid on the other
end
Translation Initiation
• mRNA joins small sub-unit of ribosome
with “start” tRNA (methionine) on it
• Small sub-unit moves along mRNA until
AUG codon on mRNA joins UAC anticodon on tRNA
• Large sub-unit joins small and ribosome
moves along mRNA one codon at a time
• tRNAs bring amino acids based on base
pairing and polypeptide chain grows
Translation
Translation animation
• http://highered.mcgrawhill.com/sites/0072507470/student_view0/
chapter3/animation__how_translation_wor
ks.html
Post-translation
• The product of translation is a chain of amino
acids called a polypeptide.
• This polypeptide is the primary structure of the
eventual protein.
• The 20 different amino acids have different
chemical properties based on their side chains.
• Some are hydrophobic; some are hydrophilic;
some are negatively charged; some are
positively charged
Post-translation
• Because of their different properties they
bend into a secondary structure then fold
over on each other into a tertiary
structure until they become functional
proteins.
• Some proteins require two or more
polypeptides to join together to achieve full
function. This would be its quaternary
structure.
Functional Protein Structure
Functional Structure of
Genetic Code Charts
Genetic Code Charts - Circular
Genetic Code
• There are 64 (43) ways for the 4 nitrogen bases
to be assembled in groups of 3.
• There are only 20 amino acids
• So the code is redundant, that is, there is more
than one codon that codes for a particular amino
acid. This property is referred to as the
degeneracy of the code
• There is no ambiguity, however. Any particular
codon only codes for one amino acid (or stop)
Mutations
• Replication, transcription and translation
are remarkably efficient and accurate
given how often they must occur.
• The occasional mistake in the placing of a
nitrogen base, however, is referred to as a
mutation.
• Because the code is redundant some
mutations don’t result in a change in the
protein
Point Mutations
• A point mutation, or
single base
substitution,
depending on where it
is, might not change
the resulting protein.
• This is particularly
true if the third base
of the triplet or codon
is involved.
Point Mutations
• Some point mutations will change the protein
Frame shift mutations
•
•
•
•
Frame shift mutations occur in two ways
An insertion means a base was added
A deletion means a base was removed
Either way it shifts the frame of how the
message is read and almost always
radically changes the protein
Frame shift mutations
Effects of Mutations
• As you have seen mutations might have
no effect.
• They might make the resulting protein less
effective.
• They might make the resulting protein not
work at all.
• They might make the resulting protein
work better. This is the basis of evolution.
Back to Diabetes
• Type 1 diabetes is a result of the pancreas failing to
produce the protein insulin.
• Type 2 diabetes is a result of a failure of many body cells
to properly produce the surface receptor proteins that
allow insulin to allow glucose into those cells.
• Neither of these processes are completely understood
as there are numerous regulatory proteins involved.
The failure of any of them could result in downstream
effects.
• Only further research will clarify the causes and effects
of the production or non-production of these proteins