1. DNA: The Molecule of Heredity Ch. 11

2. 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?

3. 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.

4. 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).

5. 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.
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?

6. 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

7. What is the Structure of DNA?
Deoxyribonucleic acid: hereditary information of all living cells
polymer composed of nucleotides:
phosphate
sugar  deoxyribose
1 of 4 bases:
Adenine (A)
Thymine (T)
Guanine (G)
Cytosine (C)

8. 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

9. 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

10. Complementary base pair & Chargaff’s Rule #A = #T #C = #G
Antiparallel strands
1 end  ‘free’ or unbonded
phosphate (5’)
sugar ) (3’)
Complementary base pair
& Chargaff’s Rule
#A = #T
#C = #G
Size of bases
A & G – 2 fused rings
(large-Purines)
C & T - single rings
(small – Pyrimidines)
rungs are same width – constant diameter

11. Hydrogen bonds between complementary bases hold 2 DNA strands together

12. 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.

13. 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

14. 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

15. 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

16. 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

17. 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 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.

18. 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
at 9min mark – lagging strand replication

19. Activity: http://www. learnerstv. com/animation/animation. php
1. How does DNA replication differ in Prokaryotes vs. Eukaryotes?
2. How do the 3 DNA Polymerases differ from each other?
How do the enzymes helicase and gyrase (or DNA topoisomerase II) work together?
What are the roles of primase and RNA primer in DNA Replication?
When does the enzyme ligase start to function?

20. 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?)

21. 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.

22. 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

23. 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

24. 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

25. 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.

26. 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 7-pound dumbbell in each hand with his arms full extended horizontally out to his sides.