Molecular Genetics A Introduction 1 Trait a characteristic

Molecular Genetics

A. Introduction 1. Trait: a characteristic produced by an organism’s proteins 2. Genes: a piece of a chromosome consisting of a DNA sequence that codes for a specific trait (protein synthesis). 3. Alleles: different forms/versions of a gene Example Gene: flower color Alleles: purple and white

4. Chromosome: Super-coiled strand of DNA v DNA only coils into dense chromosomes during Mitosis & Meiosis

a. Single-Stranded Chromosome: 1 strand of DNA b. Double-Stranded Chromosome: 2 identical strands of DNA, held together at one point (results after DNA replication)

B. DNA Structure 1. DNA is a large molecule (nucleic acid) made up of many nucleotides 2. Nucleotides consist of 3 parts: a) 1 sugar (deoxyribose) “Backbone” b) 1 Phosphate group c) 1 Nitrogenous base (Adenine, Thymine, Cytosine, Guanine)

3. DNA consists of 2 strands that look like a twisted ladder, called a double helix a) DNA Structure figured out by Watson & Crick in 1953 b) The 2 strands are held together between the base pairs by Hydrogen Bonds c) Base pairing: A-T and G-C “At The Grand Canyon” *The order of bases in the genes of a chromosome determines an organism’s proteins & traits.

A T base C phosphate G sugar G C

Base s o h P e t a ph r a Sug Nucleotide Hydrogen Bonds

C. DNA Replication 1. DNA replicates when cells are getting ready to reproduce/divide (mitosis & meiosis).

2. Multiple enzymes are involved in DNA replication. 3. Steps: a. DNA Helicase unwinds and unzips double helix between base pairs – Hydrogen bonds broken b. Single-stranded binding proteins keep strands separate during replication

c. Each original strand serves as a template d. DNA Polymerase attaches free-floating nucleotides to their base pairs on each template e. Result: 2 identical strands of DNA

DNA Polymerase Template Strand T AT A C GC G G C T AT A A T C GC G DNA Polymerase Template Strand

A C C T A G T G

D. Protein Synthesis 1. RNA Structure: • Single-stranded • Ribose (sugar) • Contains Uracil instead of Thymine

2. Protein Synthesis Process: a. Transcription (m. RNA synthesis) • A portion of DNA (a gene) “unzips” (Hydrogen bonds broken) • RNA Polymerase (enzyme) synthesizes Messenger RNA (m. RNA) by attaching free floating RNA nucleotides to only one of the DNA strands (template) *A binds to T, U binds to A, G binds to C, C binds to G • Newly formed m. RNA molecule detaches from template and DNA “zips up” again.

A T C G DNA strand “template” U RNA nucleotide

A T C G U A

A U T A C G G

A U T A C G

A U T A C G G C

A U T A C G G C Original DNA strand (TEMPLATE) New RNA strand

RNA Polymerase Template Strand U AT C GC G U AT A C GC

b. Translation (decoding m. RNA to make a protein) • m. RNA leaves the nucleus and goes to a ribosome • Each codon (3 bases) is read, one at a time • Transfer RNA (t. RNA) molecules AUG UCC AAG contain anticodons complementary to each codon, and carry specific CODON amino acids to those codons

• The amino acids bind together to form a polypeptide (protein) *The sequence of DNA bases controls the sequence of amino acids. * *The sequence of amino acids controls the shape and function of the protein. *

UAC AUG CAA GGU UAC CUA GAG UGA ACG

GUU UAC AUG CAA GGU UAC CUA GAG UGA ACG

GUU AUG CAA GGU UAC CUA GAG UGA ACG

CCA GUU AUG CAA GGU UAC CUA GAG UGA ACG

CCA AUG CAA GGU UAC CUA GAG UGA ACG

AUG CAA GGU UAC CUA GAG UGA ACG

AUG CAA GGU UAC CUA GAG UGA ACG

GAU AUG CAA GGU UAC CUA GAG UGA ACG

CUC GAU AUG CAA GGU UAC CUA GAG UGA ACG

CUC AUG CAA GGU UAC CUA GAG UGA ACG

ACU CUC AUG CAA GGU UAC CUA GAG UGA ACG

ACU AUG CAA GGU UAC CUA GAG UGA ACG

UGC ACU AUG CAA GGU UAC CUA GAG UGA ACG

UGC AUG CAA GGU UAC CUA GAG UGA ACG

UGC AUG CAA GGU UAC CUA GAG UGA ACG

AUG CAA GGU UAC CUA GAG UGA ACG

Amino acid chain t. RNA anticodon m. RNA ribosome codon

Example Problem DNA = TACGCCTAAATC m. RNA = AUGCGGAUUUAG Codons: AUG CGG AUU UAG Amino Acids: MET – ARG – ILE - Stop Start (Methionine) – Arginine – Isoleucine - Stop

Sample Problem DNA = TACTAACGGATT Find m. RNA, separate into codons, and find the corresponding amino acids to make a protein.

DNA = TACTAACGGATT m. RNA = AUGAUUGCCUAA Codons: AUG AUU GCC UAA Amino Acids: MET-ILE-ALA-Stop Start (Methionine) – Isoleucine – Alanine - Stop

E. Gene Mutations 1. Mutation- a change in the genetic material of a cell. • May lead to the production of an abnormal protein. 2. Mutations may be caused by errors in replication or by physical/chemical factors (Ex. X-rays, UV rays, etc. ) 3. If a mutation occurs in a gamete (sex cell), it may be transmitted to offspring.

4. Types of Mutations: a) Substitution: The replacement of a pair of nucleotides by another one. • May or may not alter the amino acid sequence. Example: DNA: Normal DNA TAC GCA TGG AAT m. RNA: AUG CGU ACC UUA Met Arg Thr Leu Mutated DNA substitution Mutated DNA TAC GTA TGG AAT TAC GCT TGG AAT AUG CAU ACC UUA AUG CGA ACC UUA Met His Met Arg Thr Leu Protein may not function Protein unaffected substitution

b) Insertion (addition) and Deletion (loss) of nucleotides in a DNA sequence, causing a frameshift • Very dramatic results Example: Insertion Normal DNA insertion Mutated DNA: TAC GCA TGG AAT TAT CGC ATG GAA T m. RNA: AUG CGU ACC UUA AUA GCG UAC CUU A Met Arg Thr Leu Ile Ala Tyr Leu shift

Sickle-Cell Anemia

Tay-Sachs Disease progressive deterioration of nerve cells and of mental and physical abilities (starts around 6 months of age & usually results in death by age 4 (autosomal recessive)

Cystic Fibrosis Abnormal transport of Cl- and Na+ in lungs, liver, pancreas, intestines thick mucus difficulty breathing, frequent lung infections, digestion problems (autosomal recessive)

F. Gene Regulation and Environmental Influence 1) Different genes are “turned on” or “expressed” in different types of cells a) This is why multicellular organisms are composed of many different types of cells – all with the same DNA.

b) Cell differentiation activates specific genes in the different cell types. Ex. The active genes in a cardiac cell are not all the same as those in a liver cell.

2) Environmental conditions may influence the expression of genes. a) Certain genes may be “turned on” or used more often in the presence of particular chemical or physical stimuli. Exposure to sunlight = tanning (increase in production of the pigments melanin). WARNING:

Ex. Fur color of the Himalayan rabbit and Siamese cat How YOU doin? I’m cold!