DNA
Unit 3 is all about genes, genetics, and DNA. The topic of genetics in a course on mood-altering drugs is particularly important because people inherit different abilities to respond to these drugs.
Because genes encode proteins, and some critical proteins for our study are receptors and enzymes, the VERSION of these receptors and enzymes can influence how we respond to drugs. Which version of these proteins we make is entirely determined by the combination of genes we inherited from our parents. To get in to the topic of genes and genetics, we will start with a lesson on the DNA molecule. Keep in mind, the nature of the DNA molecule was only understood in 1957 with the description of it structure. But we understood the role of this molecule in inheritance for much longer than that. In some ways, it’s an amazing thing that before understanding the DNA structure and even before knowing about chromosomes, the laws of inheritance were so accurately understood.
After successfully completing this lesson you will be able to:

Recognize the four DNA nucleotides and the rules of base pairing

Understand how the properties of DNA enable us to isolate and study it

Understand what “alleles” are and how they result in different protein functionalities

Recognize how a four letter DNA code can give rise to the diversity of cellular function and diversity of life
o Your ideas
 Who correctly identified the DNA double helix as the structure of DNA? Whose DATA did they use?
 What are the four nucleotides that comprise all DNA?
 The DNA double helix has what charge (and on what functional group)? o Previously learned material
 There are several versions of the gene that encodes the CYP3A4 enzyme. Would a version that makes “strong” CYP3A4 or “weak” CYP3A4 give someone more side effects from prescription medications? o DNA in the news
 Visit the class forum on DNA in the news. Describe what you learned at the video link recommended to you in the lesson introduction
( http://www.dnalc.org/resources/dnatoday/index.html
). Try to tell the take-home message in JUST
TWO SENTENCES. Once you have submitted your sentences, you’ll be able to see what classmates found interesting and what they learned at the DNA in the news video site they visited.
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DNA
1.
What features of DNA make it easy to isolate?
2.
What features of DNA make it ideal as the carrier of genetic diversity?
3.
How can only FOUR subunits encode so much genetic diversity?
4.
What is the relationship between DNA and protein?
5.
What is the relationship between gene and allele?
6.
What are the blood type alleles and how do they differ from each other? (or hemoglobin)
Key Terms

Nucleotide (monomer)

Nucleic acid (polymer)

Covalent bonds

Base pairs

Hydrogen bonds

Complementarity

Introns

Codons

Transcription

Translation
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
Protein
Amino acid

Allele

Polar
Please view the video found at http://www.youtube.com/watch?v=qy8dk5iS1f0 for more detail, you might also view http://www.youtube.com/watch?v=ZGHkHMoyC5I&feature=related
As you watch, keep in mind these guiding questions:

What portions of the DNA are found in the “backbone”?
 What holds the two halves of the helix together?

Which bases associate with each other to hold together the two halves of the double helix?

How can four subunits result in variation between species?
TEST OF CONTENT
Which portion of the DNA molecule is charged, and what is that charge?
Imagine you have a piece of double stranded DNA that is 15% A nucleotides. How much (in percent) of this piece is made up of G nucleotides?
Next, view the video found at http://learn.genetics.utah.edu/content/begin/tour/ . Select the “What is a Gene” tutorial tab. Keep in mind these guiding questions as you listen.

What is the relationship between genes and proteins?

List four or five different protein/ protein types that are encoded by genes.
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DNA
Next, view the video found at http://www.dnalc.org/resources/3d/chr11.html
. There is a lot of information about the genes in a particular region and you do not need to memorize any of these. As you watch, consider what you are learning about:

The relationship between chromosomes and genes

The relationship between genes and DNA

What are exons and introns?

How long is an average gene?

What are found in “intragenic”, non-coding DNA regions?
You will isolate DNA from one of many different food types in laboratory. As you do this, keep in mind what PROPERTIES of DNA allow you to separate it away from other cellular material.
TEST OF CONTENT
Why is salt used in isolation of DNA?
It makes the DNA more soluble in water
It makes the DNA less soluble in water
It does not change the solubility, but increases stability
Why is ethanol used in isolation of DNA?
It is less polar than water, thus the DNA (polar) is less soluble in ethanol
It is more polar that water, thus the non-polar DNA is more soluble in ethanol
It does not change the solubility, but increases stability
monomer polymer
Imagine a train. It is composed of many connected cars. Each car is a subunit, or in biology terms, it is a monomer. When the subunits are put together, the larger molecule is called a polymer.
The order of “cars” in the “train” will determine the function of a biological polymer. In comparison with the polymer above, this polymer will have a different functional ability:
DNA is an example of a biological polymer. Its functionality depends upon the order of monomer subunits that are added on to the strand. The DNA strand, like the train analogy, is organized by linearly arranged monomers. RNA and protein, two other biological molecules are polymers. Strong bonds hold the
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DNA monomer units together. These bonds result from the sharing of electrons – they are covalent bonds.
The DNA polymer is unique among these in that there are TWO strands that join together to make a double molecule – a double helix. The bonds that hold the two strands together are weak bonds. Hydrogen bonds join A to T and C to G. A and T nucleotides are COMPLEMENTARY to each other. Their chemical and physical structures match. Hydrogen bonds are only able to form between the complementary base types. It might seem counterintuitive that weak bonds hold the two strands together, but because each DNA strand is very long, there are a LOT of weak bonds involved and therefore there is strength in numbers. Additionally, these weak bonds can be pulled apart which is necessary for DNA to be transcribed and replicated.
The scientists who were trying to determine what biological molecule was the molecule of heredity originally favored protein. There are 20 amino acids and only four nucleotides. How could four nucleotides carry enough information to encode for the diversity of genes in diverse organisms? To think about why this is not a problem for a DNA code, consider binary code, 0 vs. 1. This simple binary code allows for a LOT of diverse functionality! The key is in the length of the strand of information. DNA molecules are VERY long. There are four options for a 1-nucleotide long DNA molecule. There are 16 options for a 2-nucleotide long DNA molecule: AA, AT, AC, AG, TA, TT, TC, TG, CA, CT, CC, CG, GA, GT, GC, and GG. How many different combinations are possible if the DNA is 12 nucleotides long?
Visit the video found at http://www.dnalc.org/resources/3d/25basepairing.html
to hear James Watson talk about these subunits and how he and Crick imagined the ways they might interact to give a molecule with known properties.
Each of the four nucleotides has three parts, a phosphate group, a deoxyribose sugar, and a nitrogen-containing base.
While the phosphate and sugar are identical in every DNA nucleotide, the nitrogen base can be of four types. The structure of the nitrogen-containing base above shows that it is adenine (A).
The four bases are:
Adenine (A)
Thymine (T)
Cytosine (C)
Guanine (G)
The diagram shows how atoms on adenine interact with those on thymine to form hydrogen bonds (2). Cytosine and guanine base pairs form three hydrogen bonds.
The specific structures of these nucleotides is not essential to understand for this course, but seeing them often helps a learner understand why there are specific interactions.
TEST OF CONTENT
What portion of a nucleotide gives each of the four its unique identity?
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DNA
Nitrogen-containing base
Deoxyribose
Ribose
Phosphate
What would be the physical comparison between a stretch of DNA that is 30% GC vs. another that is
60% GC?
The stretch with 60% GC will have more possible combinations
The stretch with 60% GC will have more non-coding regions
The stretch with 60% GC will have more negative charge
The stretch with 60% GC will be more tightly bound to its complementary strand
Visit http://learn.genetics.utah.edu/content/begin/dna/builddna/ and build a DNA molecule
Nucleotides comprise genes. Genes are long sequences of nucleotides that function together to create a product. Gene length can vary tremendously, from a few hundred nucleotides up to several hundredthousand nucleotides. Not all of nucleotides in a gene are coding for this product, some of them are necessary elements that ensure proper regulation of that gene.
In the schematic below, gray areas are portions of a gene that do code for a product, and white portions are ones that will not be converted into product. Notice that some of these “non-coding” sequences are interspersed with coding regions, these are called “introns”. Some are found in an area of the gene that helps that gene be turned on, expressed, in particular cells at particular times. ALL our cells have the same DNA, but not all the cells utilize ALL of the genes. Retinal cells need to make rhodopsin to allow them to be light sensitive. Your liver does not need rhodopsin, thus the gene specifying this protein is turned “on” in retinal cells, and “off” in liver cells.
Regulatory sequences
Introns
There are a couple of reasons to tell you about these non-coding regions. One reason to know about them is that they take up a lot of room in our DNA genome (much more room than coding sequences). But a more important reason to know about regulatory sequences is to learn that as we expose ourselves to drugs, our body adapts, in part, by changing the expression of our genes. We make MORE alcohol metabolizing enzyme when we regularly expose ourselves to alcohol. This happens by increasing the transcription of the gene that encodes for the alcohol metabolizing enzyme.
TEST OF CONTENT
How does gene regulation relate to tolerance (unit 1)?
DNA is the _stored_ form of our genetic information. Just as books in a library are useless unless they come
OUT of storage, the information in DNA must be read and used. DNA information is first transcribed into an
RNA intermediate. RNA is ribonucleic acid (and thus is quite similar in its make up to deoxyribonucleic acid).
The RNA intermediate is translated into protein. Transcription is used to describe going from the DNA code to the RNA intermediate because the same “language”. Both DNA and RNA are made up of nucleotides.
Translation describes taking this nucleotide code and decoding it into a new language – the language of amino
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DNA acids. Like DNA, proteins are polymers made up of monomer building blocks. For a protein, the building block is an amino acid.
Each amino acid is specified by three DNA nucleotides, a codon. For instance, TAC in DNA will specify AUG in RNA (RNA uses the uracil nucleotide rather than thymidine). And AUG in RNA specifies the amino acid methionine.
If you would like to know more about transcription and translation, visit this video http://www.youtube.com/watch?v=_qAIE4qMTSQ&feature=related What you do need to understand is that when the DNA is different, from one gene to another or between individuals, the protein that the gene specifies is different.
TEST OF CONTENT
What is the relationship between DNA and protein?
The order of DNA’s amino acids help direct the order of protein’s nucleotides.
The order of DNA’s nucleotides help direct the order of protein’s amino acids.
DNA’s nucleotides become mutated into amino acids.
DNA’s amino acids become mutated into nucleotides.
View the video found at http://www.youtube.com/watch?v=9UpwV1tdxcs
As you watch, consider these guiding questions:

Why does a change in the hemoglobin protein result in sickled cells?

What type of change in the DNA causes sickle cell anemia?
An ALLELE is a version of a gene. In sickle cell, the codons of the non-anemia allele read:
CTG ACT CCT GAG GAG AAG TCT
(Note – it is common to give only one half of the DNA double helix sequence when describing a gene sequence. The other half is inferred because of base pairing rules).
The sickle cell allele reads:
CTG ACT CCT GTG GAG AAG TCT
This single nucleotide difference makes the difference in the way the hemoglobin protein folds, clumps, and functions.
TEST OF CONTENT
If a DNA sequence reads TAC TAC TAC TAC (improbable to be sure), AND if a person had a genetic variation that read TAC TA TAC TAC (loss of the second “C”), how would this influence the protein made?
Required Reading
Any introductory Biology text book
Chapter or section on DNA (molecular structure and properties)
Chapter or section on genes
Internet
 http://www.dnalc.org/resources/dnatoday/index.html
(DNA in the news)
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DNA
 http://www.youtube.com/watch?v=qy8dk5iS1f0 http://www.youtube.com/watch?v=ZGHkHMoyC5I&feature=related
 http://www.dnalc.org/resources/3d/chr11.html
 http://www.dnalc.org/resources/3d/23-dna-unzip.html
Supplemental Reading
Internet
 http://www.dnalc.org/resources/3d/09-how-much-dna-codes-for-protein.html
(non-coding DNA : coding DNA)
 http://www.dnalc.org/resources/3d/10-triplet-code.html
(to think about the triplet code of DNA – to – protein)
 http://www.dnalc.org/resources/3d/12-transcription-basic.html
(animation for transcription)
 http://www.dnalc.org/resources/3d/15-translation-basic.html
(animation for translation)
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