General Biology – Unit Two
Objective Six
Let’s begin this area of study with a
look at some triviaJ
- Within each human cell (so
small one must use a microscope to see the cell) is a nucleus that contains
approximately 3 feet of DNA. This DNA is made up of 3,000,000,000
nucleotide pairs (or 6,000,000,000 nucleotides).
- The human body is made up of
approximately 50,000,000,000,000 cells. Each cell contains these same
6,000,000,000 nucleotides.
- So. . .how did each cell
acquire this set of DNA? - Through DNA replication. Before each
cell divides, the DNA has to make a complete copy of itself.
- To make an entire human
composed of 50 trillion cells, the DNA must have replicated 50 trillion
times.
- 6,000,000,000 X
50,000,000,000,000 = 300,000,000,000,000,000,000,000 or 3.0 X 1023
- Can anything be copied 3.0 X
1023 times without making a mistake?
- The answer is NO, NO,
NO!!!!
- MISTAKES HAPPEN! A mistake
in the DNA is known as a mutation.
Here’s a little more trivia.
- If we have 50 trillion cells
and each cell contains 3 feet of DNA, 50 trillion / 5280 = 10 billion
miles of DNA within the cells of each person!
- To keep up with red blood
cell production, each person produces 25,000,000 red blood cells a second!
- 25,000,000 X 3ft. =
75,000,000 ft. of DNA produced each second (just for our red blood
cells)
- 75,000,000/5,280 = 14,204
miles of DNA/second
- The moon is 230,000 miles
away from the Earth.
- 230,000/14,204 = 16.9 seconds.
IN 17 SECONDS, YOU PRODUCE ENOUGH DNA (JUST MAKING RED BLOOD CELLS) TO
STRETCH TO THE MOON:)
- Just going by statistics, a
mutation shows up about every third cell division (DNA Replication).
- Besides occurring naturally
at a relatively predictable rate, other agents can trigger mutations.
These are known as MUTAGENS.
- Examples of mutagens would
include certain chemicals, radiation and even viruses. http://www.ultranet.com/~jkimball/BiologyPages/D/DNArepair.html
When would the majority of mistakes in the DNA happen? Well . . .when is the
most DNA being produced? . . .During DNA Replication.
- To review the process of DNA
Replication:
- The hydrogen bonds between
the nitrogen bases break and the two sides of the DNA separate from each
other.
- Enzymes bring corresponding
nucleotides to the exposed nitrogen bases to build two new sides.
In theory, these bases should match up A=T, C=G, but that doesn’t always
happen – MUTATIONS OCCUR!
For example: Let’s say you have a strand of DNA with hundreds of nucleotide
pairs. We are going to focus on what happens to a base pair triplet in the
middle of our strand of DNA.
|
C:G
T:A
C:G
|
C G
T A
C G
|
C:G
T:A
C:G
|
C:G
A:A*
C:G
|
|
This would represent the base triplet in our original DNA.
|
This would represent the two sides of the DNA separating.
|
The diagram above would indicate the two strands of DNA that formed as a
result of replication.
*NOTICE THE MISTAKE IN THE STRAND ON THE RIGHT!
|
- Where this becomes
important, is the production of the protein from the code on the DNA. If we
are coding from the strand on the left side – the original (correct)
code is CTC. CTC in DNA codes for GAG in mRNA, which codes for the
amino acid Glutamic Acid.
- However, if a protein were
being coded from the DNA with the mistake (CAC), this would code for GUG
in mRNA, which codes for the amino acid Valine.
- This type of mistake, which
results in the misreading of only one base triplet, and affects only one
amino acid in the entire protein, is known as a point or substitution
mutation.
- Let’s briefly consider the
ramifications if the mutation occurred in the third nitrogen base of the
triplet we are looking at. Remember CTC is the correct code for the strand
on the left side of our DNA. If a mistake occurred that resulted in CTT,
let’s see what would happen. CTT in DNA codes for GAA in mRNA,
which codes for the amino acid Glutamic Acid.
- Do you see what happened?
You had a mutation that still coded for the same amino acid. If the amino
acid doesn’t change, you would never notice the mutation.
- Point or Substitution
Mutations will change a protein by ONE amino acid or by NONE!
- Since proteins are made
of lots of amino acids, changing one usually does not cause the
protein to become nonfunctional. Usually, point mutations are not
terribly serious, and are really quite common.
I am going to give you an example of a genetic disorder caused by a point
mutation that is quite serious. Hemoglobin is a large protein molecule found in
red blood cells. Its job is to carry oxygen. The hemoglobin protein is made of
573 amino acids. There are different forms of hemoglobin that have resulted
from different point mutations. Most of these forms of the hemoglobin still
function fine, but one form that has a VALINE instead of GLUTAMIC ACID in the
6th position does not function correctly. Apparently this is a critical
location for determining hemoglobin shape. Individuals that have this mutation
have the condition known as Sickle Cell Anemia.
In Sickle Cell Anemia, the hemoglobin is sickled. This causes the red blood
cells to be pulled out of shape. This results in a host of problems; ranging
from anemia and lassitude, to problems caused by blood cells clogging various
body organs. We will look at sickle cell anemia in more depth in the 3rd
unit. For now, just realize that Sickle Cell Anemia is an example of a serious
genetic disorder that is caused by a point mutation.
Now to examine some other types of mutations, let’s look at how the code is
read. The code is read in sets of three nucleotides so in a way, it’s like
reading sentences of three letter words.
- Does this sentence make
sense? THE FAT CAT RAN FAR. (Other from the standpoint of
wondering whether a fat cat could run very far, it should make sense.)
- Let’s say that we change one
letter – THE FAT RAT RAN FAR. (It may have changed the meaning of
the sentence slightly, but there is still some meaning in the sentence).
(This is like a substitution mutation.)
- Now let’s say that we remove
a letter – We still have to read the sentence in sets of three letters
(that’s the way DNA works). What happens, is the entire sentence is
shifted over. THE ATC ATR ANF AR. Does this sentence make sense? I
hope you said "NO!" This is an example of a deletion mutation.
When one nucleotide is removed, the reading of the entire code is shifted
over.
- A Deletion mutation
is an example of a Frameshift mutation. In Frameshift mutations,
the entire code is disrupted and so commonly one of two things will
happen: The protein will not be made or the protein will be
built but it does not function.
- Another possibility is that
a letter is read twice or copied twice – THE FFA TCA TRA NFA R.
This is an example of an insertion mutation. Does this sentence
make sense? Hopefully, you said "NO – again!"
- An Insertion mutation
is another example of a Frameshift mutation. Once again, it will
result in either a protein not being built or being built and having so
many incorrect amino acids that it will not function.
- Frameshift mutations are
almost always more serious than substitution mutations.
- http://www.ultranet.com/~jkimball/BiologyPages/M/Mutations.html
Let’s look at an example of a frameshift mutation that is very common in
humans. Do you ever go outside? Some folks enjoy walking in the sunshine,
playing sports, gardening or doing other activities outside. One of the causes
of mutations is radiation, and sunshine has a type of radiation known as
Ultraviolet radiation or U.V. radiation. When U.V. light strikes your skin, it
penetrates to the cells in the skin and anytime this radiation encounters two
thymine nucleotides that are side by side in the DNA, it causes them to stick
together.
- This creates a mutation
known as a Thymine Dimer.
- When two thymines are stuck
together, a couple of things can happen; the DNA may not be read to build
a protein, or the thymines may be read as only one (a deletion mutation).
- This type of problem is
associated with causing skin cancer.
- Now, every time a person
goes outside into the sunlight – they get thymine dimers. You have had a
bunch! My question is . . .Why doesn’t everyone have skin cancer?
The answer is because we have an enzyme repair system. A
wonderful thing! One set of enzymes travels up and down the DNA strand
searching for bulges – mistakes. When a mistake is located, the enzyme cuts the
faulty DNA away. Another enzyme brings the correct nucleotides in the attach to
the DNA strand and another enzyme "sews" the new DNA in place. This
happens constantly along the DNA in all of your cells, and so – for the most
part, these dimers don’t cause us problems. Of course, too many dimers (too
much U.V.) can overtake our repair system and still lead to skin cancer.
http://www.nih.gov/sigs/dna-rep/whatis.html
There is a genetic disorder called Xeroderma pigmentosum in
which the individuals do not have this enzyme repair system. It is very serious
and the folks that have this often die from skin cancer at a young age. You may
have read or seen on TV television shows about these little kids that cannot go
out into the sunlight. They even have to keep the lights dimmed in their homes.
It makes one appreciate how effectively our body’s work, when they do work
correctly.
· http://www.xps.org/
Our final topic in looking at mutations is chromosomal mutations. All
of the previous topics have dealt with single gene mutations. But how many
genes are on a chromosome? Lots. So if a chromosome is broken – there is the
potential for very serious mutations. When chromosomes break, a piece may
become lost, a piece may reattach to another chromosome, a piece may become
inverted and reattach. Any of these can result in lethal problems.
- A good example to study
when looking at chromosomal mutations is what happened as a result of the
nuclear accident at Chernobyl, Russia. When this accident occurred,
those closest to the reactor died (they had the greatest amount of
chromosomal damage). Others that were further away from the accident,
developed radiation sickness and later died and even within a few hundred
miles, there was a much higher incidence of cancer and birth defects.
- http://www.nea.fr/html/rp/chernobyl/c05.html