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

Deoxyribonucleic acid: hereditary information of all living cells

polymer composed of nucleotides:1. phosphate2. sugar deoxyribose3. 1 of 4 bases:

• Adenine (A) • Thymine (T)• Guanine (G)• Cytosine (C)

What is the Structure of DNA?

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 researchand 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 = #Ghttp://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

https://www.youtube.com/watch?v=5qSrmeiWsuc

Replication fork

• 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

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?

Activity: http://www.learnerstv.com/animation/animation.php?ani=169&cat=biology

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

http://blogs.scientificamerican.com/guest-blog/2013/06/14/the-man-of-steel-myostatin-and-super-strength/