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of
Nucleic
Acids
&
Nucleic Acids
Miss Crimson: Good day, ladies and gentlemen of the jury. My name is Miss Crimson, and I'm here to prove to you
without a shadow of a doubt that my client, Colonel Custard, is not guilty of the most heinous crime of murdering poor
Mr. Bones. The host of the International Cookbook Writers Convention was cruelly murdered with a lead pipe in a
spiral staircase while on his way to deliver his award-winning cookbook to the kitchen. However, the defendant,
Colonel Custard, was not responsible. The testimony of my expert witness will not only clear my client of all wrongdoing but will also reveal the identity of the true killer of our poor departed Mr. Bones.
Your honor, I call to the stand Professor Pear, an expert in DNA structure and function! Professor, could you please
explain to us what DNA is?
Professor Pear: Why, yes. I'd be happy to tell you about DNA. DNA stands for 'deoxyribonucleic acid,' and it's a
fascinating molecule. It's one of two basic types of nucleic acids, the other being RNA, or 'ribonucleic acid.'Nucleic
acids are the molecules that cells use to store, transfer and express genetic information.
Miss Crimson: So, you're saying that everyone has this DNA stuff inside his or her body?
Phosphodiester Bonds
Oh, um, did I forget to tell you what a polynucleotide is? A polynucleotide is simply a long chain of nucleotides. 'Poly' means 'many', so 'polynucleotide' literally means 'many nucleotides.' Now, you're probably wondering how these
nucleotides are held together. Nucleotides in a polynucleotide molecule are held together by the bond between the
phosphate group of one nucleotide and the sugar of a second nucleotide. A hydroxyl group (or -OH) in the sugar and
one of the oxygen atoms in the phosphate group form what's called a diester bond. For this reason, the bond between
the phosphate group and the sugar in a polynucleotide molecule is called aphosphodiester bond.
Linking nucleotides together forms a structure that looks like half of a ladder that was cut down the middle with an
axe. The phosphate groups and sugars form the backbone of the ladder, while the nitrogenous bases provide the
rungs. There are four different types of nitrogenous bases, and the order of the bases in a polynucleotide is what tells
a cell how to make a structural protein, an enzyme or any other number of important components of a healthy,
functioning organism.
Lesson Summary
Miss Crimson: Okay, Professor Pear, let me stop you right there. You've been throwing around a lot of fancy jargon.
Before you go any further, let me see if I can summarize for the jury what you've told us so far.
Nucleic acids are the molecules cells use to store, transfer and express genetic or hereditary information. Nucleic
acids can be categorized into DNA, or deoxyribonucleic acid, and RNA, or ribonucleic acid. DNA is the molecule that
stores genetic information in an organism.
A single monomer subunit of a nucleic acid is called a nucleotide. A DNA nucleotide is composed of a sugar,
called deoxyribose, a phosphate group and a nitrogenous base. A polynucleotide is a nucleic acid molecule
consisting of a long chain of nucleotides. Nucleotides in a polynucleotide molecule are held together by a bond
between the phosphate group of one nucleotide and the sugar of a second nucleotide, which is called
aphosphodiester bond.
Thymine
&
Professor Pear: You're quite right. The bases can be categorized into two different groups. The single-ring nitrogenous
bases, thymine and cytosine, are calledpyrimidines, and the double-ring bases, adenine and guanine, are
called purines. (Miss Crimson has a puzzled look.) I guess you might wonder how I can remember that, but it's really
quite simple. 'All Gods are pure.' Adenine and guanine are purines. And, by process of elimination, that means
cytosine and thymine have to be pyrimidines. See?
Miss Crimson: Yes, yes. That's a very nice mnemonic aid. Adenine and guanine are purines, but we're getting off
track. You were telling us why the chemical structure of nucleotides is important.
The sugar and phosphate ends of a DNA strand are referred to by their
carbon numbers
Remember how I said that DNA polynucleotides look like half of a ladder? Well, hydrogen bondingcompletes the
ladder. Since the nitrogenous bases can hydrogen-bond, one polynucleotide can bond with another polynucleotide,
making the nitrogenous bases the rungs of the ladder. Each polynucleotide participating in this ladder is often referred
to as a strand. Because the bases can only fit together in a specific orientation, a parallel orientation between the
strands won't work. The strands must be antiparallel, or upside-down, relative to one another.
Miss Crimson: What do you mean antiparallel?
Professor Pear: Well, remember that the backbone is made of phosphate groups and sugars. Therefore, each strand
will always have a phosphate at one end and a sugar at the other end. Rather than having to refer to the phosphate
or sugar end, scientists simply refer to the ends of the DNA by the closest carbon in the sugar ring. Since the carbons
in the sugar are numbered one to five, the sugar end of the strand is called the 3' end and the phosphate end of the
strand is called the 5' end. Remember that complementary base pairing works like a lock and key, so there's only one
orientation in which hydrogen bonding will work. If you try to orient the two strands parallel to each other, the sugar
ends of the polynucleotides are both at one end and the phosphate groups are at the other end. However, the
nitrogenous bases can't hydrogen-bond in this orientation. The key can't fit into the lock.
For hydrogen bonding to work, the two DNA strands must run in opposite directions. The 3' end of one strand can
hydrogen-bond with the 5' end of the other strand. If we represent the strands as arrows with the arrowhead at the 3'
end of the stand, we can see that the strands in a DNA molecule are organized antiparallel relative to each other.
Lesson Summary
Miss Crimson: Okay. Let me stop you again, Professor, so I can summarize your testimony for the jury.
There are four nitrogenous bases found in DNA that are called guanine, adenine, thymine and cytosine. They are
abbreviated by the first letter in their name, or G, A, T and C. The bases can be divided into two categories: Thymine
and cytosine are called pyrimidines, and adenine and guanine are called purines. Each nucleotide base can
hydrogen-bond with a specific partner base in a process known as complementary base pairing: Cytosine forms
three hydrogen bonds with guanine, and adenine forms two hydrogen bonds with thymine. These hydrogen-bonded
nitrogenous bases are often referred to as base pairs.
Because of the alternating nature of the phosphate groups and sugars in the backbone of nucleic acids, a nucleic acid
strand has directionality. The end of a nucleic acid where the phosphate group is located is called the 5' end. The end
of the nucleic acid where the sugar is located is called the 3' end. Finally, DNA strands are antiparallel, meaning
that the strands in a DNA molecule are parallel, but are oriented in opposite directions. Essentially, the 5' end of one
strand pairs with the 3' end of the other strand.
To be continued . . .
bacteria into S bacteria, Avery and his team devised a series of clever experiments. By spinning the purified sample
very fast in a machine, known as a centrifuge, fats were eliminated from the sample. Sample treated in this manner
could still transform R cells into S cells.
Shockingly, treating the sample with something that degrades protein did not affect the ability of the purified sample
to turn R cells into S cells. Treating the sample with a substance that degrades RNA also did not affect the transforming
principle. However, treating the purified sample with something that degraded DNA eliminated the R to S
transformation.
Avery concluded that the transforming principle was DNA. Today, we know that permanently changing the
characteristics of an organism can be accomplished by changing its DNA content.
James Watson, Francis Crick and another scientist named Maurice Wilkins were awarded the 1962 Nobel Prize in
Physiology or Medicine for 'their discoveries concerning the molecular structure of nucleic acids and its significance
for information transfer in living material.'
Lesson Summary
Ladies and gentlemen of the jury, you can see that the work of Fredrick Griffith and Oswald Avery establishes DNA
as the molecule responsible for transmitting heritable traits.
James Watson and Francis Crick developed the double-helix model for the structure of DNA. In short, DNA is
organized as a twisted ladder with phosphate groups and sugars composing the backbone of the strands, and
nitrogenous bases linked by hydrogen bonds make up the rungs. Each strand is oriented antiparallel to the other. With
three billion bases in humans, each person has a unique DNA sequence.
Based on the sequence of the DNA found in the blood at the scene of the crime, I contest that my client is innocent of
the murder. In fact, based on the DNA evidence, we have reason to believe that Mr. Teal murdered Mr. Bones in the
staircase with a lead pipe!
To be continued
Miss Ivory: Professor, you said that you found DNA evidence at the scene of the crime; however, you said nothing
about RNA evidence. Didn't you say that there are two types of nucleic acids? What about thisribonucleic acid,
or RNA? It seems like you've conspicuously avoided talking about RNA altogether. Is it because the lack of RNA
evidence directly links Colonel Custard to the crime?
Professor Pear: That's an excellent question. I would be remiss to talk about nucleic acids and only talk about DNA.
RNA is, in fact, the second of the two types of nucleic acids; however, there are a number of structural differences
between the two.
First let's address the name. Like DNA, RNA is a nucleic acid composed of a sugar, a phosphate group and a
nitrogenous base. One difference between DNA and RNA is the sugar. Whereas the sugar in DNA is deoxyribose,
the sugar in RNA is ribose. Now, I won't dwell on the exact chemical difference between the two sugars, but ribose
has one extra hydroxyl group compared to deoxyribose.
Second, there are four different nitrogenous bases found in DNA and RNA; however, there is one difference. The
bases found in DNA are guanine, cytosine, adenine and thymine. The bases found in RNA are guanine, cytosine,
adenine, and uracil. Uracil forms two hydrogen bonds with adenine and functions just like thymine does. It's simply
used in RNA instead of thymine.
Finally, unlike DNA, which is double-stranded, RNA is single-stranded.
The central dogma states that DNA creates RNA and RNA makes protein
As you can see, there are many types of RNA performing all kinds of interesting jobs. In fact, why don't I tell you about
why we believe RNA actually preceded DNA?
Molecular Stability
Miss Ivory: Professor, please get to the point. You've laid out very nicely that RNA plays a number of key roles in
translating the information in DNA into protein, but you have yet to provide an adequate explanation to account for the
absence of RNA evidence in your testimony.
Professor Pear: Oh, right. I'm sorry. Sometimes I just get carried away talking about nucleic acids. One of the major
roles of RNA in a cell is to make proteins and proteins carry out many cellular functions in biology; however, it's
inefficient for the cell to maintain a constant level of mRNA and protein.
Miss Ivory: Please, explain for the jury, Professor, what all this really means.
Professor Pear: Think of the electronic devices in your room. Let's say that I keep my computer on 24 hours a day
because I want to be able to do an online search whenever I feel like it. There's a cost to that practice. First, I'm going
to have to pay for the electricity to power the computer. Second, let's also say I've decided to also leave my monitor,
printer, speakers, and a number of other devices plugged in as well, so many in fact, that I'm using up all the electrical
outlets in the room.
Now, if I want to plug in a new electronic device, I will need to turn off one of my devices before I can plug in a new
one. I may be able to surf the Internet faster, but it may be at the cost of the setup time to use another device, like say
a hair dryer. If I use a lot of other electronic devices besides the computer, I might not be saving myself that much
time in the long run if I constantly have to turn off the computer to plug other things in.
An alternative strategy would be to keep all of the electrical devices off both to conserve energy and to minimize the
startup time for using any one electrical device.
The same conservation strategy applies to a cell.
If RNA was a very stable molecule, it might tie up a lot of resources in a molecule that isn't being used. For instance,
yeast consumes sugar for energy. Although there are many different types of sugar that a yeast may encounter in its
environment, it makes sense to only express the RNA and protein to consume the available type of sugar rather than
waste energy maintaining every RNA and protein required to break down every type of sugar.
DNA is more stable than RNA due to its many hydrogen bonds
For a variety of structural reasons, mRNA has a very short lifespan compared to DNA.
There are many hydrogen bonds holding a DNA molecule together. While the bases in a RNA molecule can hydrogen
bond with each other, usually far fewer bonds can form compared to a DNA molecule. Fewer hydrogen bonds means
a less stable structure.
Second, the extra hydroxyl group in the ribose sugar of RNA makes RNA more reactive than DNA. A reaction between
that hydroxyl group and another molecule could destroy the RNA molecule.
Finally, proteins that degrade RNA are found everywhere.
If you consider all of these differences in stability between RNA and DNA, you can see why RNA is harder to isolate
from a crime scene; however, even if we had isolated any RNA, consider the information we would gain from
comparing mRNA samples to DNA samples from the same person.
According to the central dogma, mRNA is merely a temporary copy of the corresponding piece of DNA. Simple
sequence analysis would yield the same results, albeit with uracil instead of thymine.
Lesson Summary
Miss Crimson: Ladies and gentlemen of the jury. I ask you to find my client, Colonel Custard, innocent of murder. The
prosecution's main argument against the DNA evidence in this trial was the absence of RNA evidence.
I believe Professor Pear has satisfactorily demonstrated that while RNA, or ribonucleic acid, is a nucleic acid like DNA,
it is both structurally and functionally distinct from DNA.
Ribose is the sugar found in RNA instead of deoxyribose like DNA. Uracil is the nitrogenous base found in RNA that
bonds with adenine instead of thymine that is found in DNA. Like thymine, uracil forms two hydrogen bonds with
adenine.
The central dogma tells us that DNA makes RNA and RNA makes protein.
Three major types of RNA are mRNA, or messenger RNA, that serve as temporary copies of the information found
in DNA; rRNA, or ribosomal RNA, that serve as structural components of protein-making structures known as
ribosomes; and finally, tRNA, or transfer RNA, that ferry amino acids to the ribosome to be assembled into proteins.
My witness has told you that RNA is inherently unstable and the central dogma states that mRNA is merely a copied
version of DNA, so lack of RNA evidence is irrelevant. The absence of my client's DNA at the crime scene and the
presence of Mr. Teal's should exonerate my client. Listen to the evidence and find my client not guilty. I rest my case.