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DNA: The Molecule of Heredity
Ch. 11
Chapter 11 At a Glance
• 11.2 What Is the Structure of DNA?
• 11.3 How Does DNA Encode Genetic Information?
• 11.4 How Does DNA Replication Ensure Genetic
Constancy During Cell Division?
• 11.5 What Are Mutations, and How Do They Occur?
Muscles, Mutations, and Myostatin
NO, THE BULL in the top photo hasn’t been pumping iron or taking
steroids – he’s a Belgian Blue, and they always having bulging
muscles. What makes a Belgian Blue look like a bodybuilder,
compared to an ordinary bull, such as the Hereford in the bottom
photo?
When any mammal
develops, its cells
divide many times,
enlarge, and
become specialized
for a specific function. The size, shape, and cell types in any organ
are precisely regulated during development, so that you don’t wind up
with a head the size of a basketball, or have hair growing on your
liver. Muscle development is no exception. When you were very
young, cells destined to form your muscles multiplied, fused together
to form long, relatively thick cells with multiple nuclei, and
synthesized specialized proteins that cause muscles to contract and
thereby move your skeleton.
A protein called myostatin, found in all mammals, puts the brakes on
muscle development. “Myostatin” literally means “to make muscles
stay the same,” and that is exactly what it does. As the muscles
develop, myostatin slows down – and eventually stops – the
multiplication of these pre-muscle cells. Myostatin also regulates the
ultimate size of muscle cells and, therefore, their strength.
Belgian Blues have more, and larger, muscle cells than ordinary
cattle do. Why? You may have already guessed – they don’t produce
normal myostatin. As you will learn, proteins are synthesized from
the genetic instructions contained in deoxyribonucleic acid (DNA).
The DNA of a Belgian Blue is very slightly different from the DNA of
the other cattle – the Belgian Blue has a change, or mutation, in the
DNA of its myostatin gene. As a result, it produces defective
myostatin. Belgian Blue pre-muscle cells multiply more than
normal, and the cells become extra large as they differentiate,
producing remarkably buff cattle.
1. How does DNA contain the instructions for traits such as muscle
size, flower color, or gender?
2. How are these instructions passed, usually unchanged, form
generation to generation?
3. And why do the instructions sometimes change?
Cell Division Transmits Hereditary Information to Each Daughter Cell
Chromosome: consists of DNA and proteins which organize its 3-D
structure and regulate its use
Genes: unit of inheritance; segments of DNA that range in length of
#’s of nucleotides
• spell out instructions for making proteins of a cell
What is the Structure of DNA?
Deoxyribonucleic acid: hereditary information of all living cells
 polymer composed of nucleotides:
1. phosphate
2. sugar  deoxyribose
3. 1 of 4 bases:
• Adenine (A)
• Thymine (T)
• Guanine (G)
• Cytosine (C)
DNA is a Double Helix of Two Nucleotide Strands
Maurice Wilkins & Rosalind Franklin (1940’s): used X-ray
diffraction technique to produce pictures of the structure of DNA
 long & thin
 uniform diameter
 helical – twisted ladder
 double helix – 2 strands of DNA
 repeating subunits
 phosphates on outside of helix
Francis Crick & James Watson:
combined X-ray data with other research
and built the first double helix model
of DNA (3/7/53)
 single strand of DNA is a polymer
of many nucleotide subunits
 sugar-phosphate backbone
 strands are antiparallel
(see next slide)
 Watson, Crick, & Wilkins received
Nobel Prize in ’62
 Franklin died in ’58 so she was not
included in award
 Antiparallel strands
 1 end  ‘free’ or unbonded
phosphate (5’)
 1 end  ‘free’ or unbonded
sugar ) (3’)
 Complementary base pair
& Chargaff’s Rule
 #A = #T
 #C = #G
http://www.dnalc.org/view/15495-Chargaff
 Size of bases
 A & G – 2 fused rings
(large-Purines)
 C & T - single rings
(small – Pyrimidines)
 rungs are same width – constant diameter
 Hydrogen bonds between complementary bases hold 2 DNA
strands together
11.3 How Does DNA Encode Genetic Information
DNA carries the genetic code in its sequence of 4 nucleotides
 DNA 10 nucleotides long can form 1 million different sequences
Different sequences encode for very different pieces of information (or no info)
 Friend / Fiend / Fliend
Case Study: Muscles, Mutations, and Myostatin
All “normal” mammals have a DNA sequence that encodes a
functional myostatin protein, which limits their muscle growth.
Belgian Blue cattle have a mutation that changes a ‘friendly’ gene to
a nonsensical “fliendly” one that no longer codes for a functional
protein, so they have excessive muscle development.
11.4 How Does DNA Replication Ensure Genetic Constancy
During Cell Division?
 Rudolf Virchow (1850’s):
“All cells come from pre-existing cells”
 Cells reproduce by dividing in half
 Each of the 2 daughter cells gets an exact
copy of the parent cells genetic
information
 DNA replication = duplication of the
parent cell DNA
• DNA replication produces 2 DNA double helices each with
1 original strand and 1 new strand
• Complementary base pairing provides a model for how DNA
replicates
• Ingredients for replication:
• Parental DNA strands
• Free nucleotides
• Variety of enzymes to unwind
parental DNA and synthesize new
DNA strands
• DNA helicase: enzyme that pulls apart parental DNA double helix
at H-bonds btwn complementary pairs
• DNA polymerase: enzyme that pairs free nucleotides with their
complementary nucleotide on each separated strand
Replication fork
https://www.youtube.com/watch?v=5qSrmeiWsuc
• Semiconservative replication: 2 resulting DNA molecules have 1
old parental strand and 1 new strand
• If no mistakes have been made, the base sequence of both new
strands are IDENTICAL to the base sequence of the parental DNA
How long does DNA replication take?
• Human chromosomes range from 50mill nucleotides in the Y
chromosome to 250mill nucleotides in Chromosome 1.
• Eukaryotic DNA copied at 50 nucleotides/sec; takes 12-58 days to copy a
human chromosome in one continuous piece. MAKE SENSE? EFFICIENT?
• Several DNA
helicases & DNA
polymerases
work to split
and copy small
pieces of the
DNA strand at
the same time.
• Since DNA polymerase always moves from 3’ (sugar-end) to 5’
(phosphate-end) and DNA strands are antiparallel, DNA
polymerase molecules move in opposite directions.
• Short lagging strands are synthesized while the helicase continues
to unwind in the opposite direction
• DNA ligase:
enzyme that ties
DNA together
https://www.youtube.com/watch?v=8kK2zwjRV0M
at 9min mark – lagging strand replication
Activity: http://www.learnerstv.com/animation/animation.php?ani=169&cat=biology
1. How does DNA replication differ in Prokaryotes vs. Eukaryotes?
2. How do the 3 DNA Polymerases differ from each other?
3. How do the enzymes helicase and gyrase (or DNA topoisomerase II) work together?
4. What are the roles of primase and RNA primer in DNA Replication?
5. When does the enzyme ligase start to function?
11.5 What Are Mutations and How Do They Occur?
• mutations: infrequent changes in the nucleotide sequence that
result in defective genes
• often harmful- can cause organism to die quickly
• Some have no functional effect
• Some may be beneficial and provide an advantage to an
organism in certain environments (basis for evolution?)
Case Study: Muscles, Mutations, and Myostatin
At the appropriate time during development, myostatin blocks the
cell cycle in the G1 phase, before DNA replication starts. Therefore,
when myostatin is present, pre-muscle cells do not enter the S phase,
and do not replicate their DNA. The cells stop dividing, limiting the
number of mature muscle cells. The mutated myostatin of Belgian
Blue cattle does not block progression
through the cell cycle. Pre-muscle
cells replicate their DNA and continue
to divide, producing many more
muscle cells than in normal cattle.
• Accurate replication and proofreading produce almost error-free
DNA
• DNA polymerase mismatches nucleotides once every 1,000 to
100,000 base pairs
• Completed DNA strands contain only about 1 mistake in every
100 mill to 1 bill base pairs
• In humans, this amounts
to less than 1 error /
chromosome / replication
• Toxic chemicals &
radiation can also
alter/damage DNA
• Types of mutations
• Point mutations (nucleotide substitutions): changes to
individual nucleotides in the DNA sequence
• Insertion mutations: when 1 or more new nucleotide pairs are
inserted into the
DNA double helix
• Deletion mutations:
when 1 or more
nucleotide pairs are
removed from the
double helix
• Types of mutations
• Inversion: when a piece of DNA is cut out of a chromosome,
turned around, and re-inserted into the gap
• Translocation: when a chunk of DNA (usually large) is
removed from 1 chromosome and attached to another
Case Study: Muscles, Mutations, and Myostatin
Belgian Blue cattle have a deletion mutation in their myostatin
gene. The result is that their cells stop synthesizing the myostatin
protein about halfway through. Several breeds of “double-muscled”
cattle have this same deletion mutation, but other double-muscled
breeds have totally different mutation. Other animals, including
several breeds of dogs, such as whippets may also have myostatin
mutations. The mutations are generally different than those found in
any of the breeds of cattle, but produce similar phenotypic effects.
All of these mutations result in nonfunctional myostatin proteins.
This fact reveals an important feature of the language of DNA: The
nucleotide words must be spelled just right, or at least really close,
for the resulting proteins to function. In contrast, any one of the
enormous number of possible mistakes will render the proteins
useless.
Humans have myostatin, too: not surprisingly, mutations can occur in
the human myostatin gene. A child inherits two copies of most genes,
one from each parent. About a decade ago, a child was born in
Germany who inherited a point mutation in his myostatin gene from
both parents. This particular point mutation results in short, inactive
myostatin proteins. At 7 months, the boy already had well-developed
calf, thigh, and buttock muscles. At 4 years old he could hold a 7pound dumbbell in each hand with his arms full extended horizontally
out to his sides.
http://blogs.scientificame
rican.com/guestblog/2013/06/14/theman-of-steel-myostatinand-super-strength/