Genetics in ~1920:1. Cells have chromosomes

Sketch of Drosophila chromosomes (Bridges, C. 1913)

Mutant phenotypesShortaristae

Blackbody

Cinnabareyes

Vestigialwings

Browneyes

0 48.5 57.5 67.0 104.5

Genetics in ~1920:1. Cells have chromosomes

2. Specific locations on chromosomes control different phenotypes

Sketch of Drosophila chromosomes (Bridges, C. 1913)

Protein

DNAChromosomes are made of:

Genetics in ~1920:

Which one is the genetic material?

DNA: consists of nucleotides

The structure of a nucleotide

1’

2’3’

4’

5’

DNA: consists of nucleotides (4 types)

The structure of a nucleotide

Purines

Pyrimidines1’

2’3’

4’

5’

Sugar–phosphate backbone

5 end

Nitrogenous bases

Thymine (T)

Adenine (A)

Cytosine (C)

Guanine (G)

DNA nucleotide

Sugar (deoxyribose) 3 end

Phosphate

DNA is a polymer

-Nucleotides are joined together by linking 5’ and 3’ carbons of sugar groups to phosphate groups

- A chain of nucleotides has a 5’ end and a 3’ end

Aminogroup

Carboxylgroup

Protein: Consists of amino acids

Nonpolar

Glycine(Gly or G)

Alanine(Ala or A)

Valine(Val or V)

Leucine(Leu or L)

Isoleucine(Ile or I)

Methionine(Met or M)

Phenylalanine(Phe or F)

Trypotphan(Trp or W)

Proline(Pro or P)

Polar

Serine(Ser or S)

Threonine(Thr or T)

Cysteine(Cys or C)

Tyrosine(Tyr or Y)

Asparagine(Asn or N)

Glutamine(Gln or Q)

Electricallycharged

Acidic Basic

Aspartic acid(Asp or D)

Glutamic acid(Glu or E)

Lysine(Lys or K)

Arginine(Arg or R)

Histidine(His or H)

Aminogroup

Carboxylgroup

Protein: Consists of amino acids (20 different types)

Peptidebond

Amino end(N-terminus)

Side chains

Backbone

Carboxyl end(C-terminus)

(a)

(b)

A polypeptide

Living S cells (control)

Living R cells (control)

Heat-killed S cells (control)

Mixture of heat-killed S cells and living R cells

Mouse diesMouse dies Mouse healthy Mouse healthy

Living S cells

RESULTS

EXPERIMENT

Griffith (1928) Transformation of bacteria

Living S cells (control)

Living R cells (control)

Heat-killed S cells (control)

Mixture of heat-killed S cells and living R cells

Mouse diesMouse dies Mouse healthy Mouse healthy

Living S cells

RESULTS

EXPERIMENT

Griffith (1928) Transformation of bacteria

Avery (1944) DNA is the transforming material

How could he have shown this?

Bacterial cell

Phage head

Tail sheath

Tail fiber

DNA

100

nm

Hershey + Chase (1952) T4 infection of E. coli

EXPERIMENT

Phage

DNA

Bacterial cell

Radioactive protein

Radioactive DNA

Batch 1: radioactive sulfur (35S)

Batch 2: radioactive phosphorus (32P)

Hershey + Chase (1952) T4 infection of E. coli

EXPERIMENT

Phage

DNA

Bacterial cell

Radioactive protein

Radioactive DNA

Batch 1: radioactive sulfur (35S)

Batch 2: radioactive phosphorus (32P)

Empty protein shell

Phage DNA

Hershey + Chase (1952) T4 infection of E. coli

EXPERIMENT

Phage

DNA

Bacterial cell

Radioactive protein

Radioactive DNA

Batch 1: radioactive sulfur (35S)

Batch 2: radioactive phosphorus (32P)

Empty protein shell

Phage DNA

Centrifuge

Centrifuge

Pellet

Pellet (bacterial cells and contents)

Radioactivity (phage protein) in liquid

Radioactivity (phage DNA) in pellet

Hershey + Chase (1952) T4 infection of E. coli

EXPERIMENT

Phage

DNA

Bacterial cell

Radioactive protein

Radioactive DNA

Batch 1: radioactive sulfur (35S)

Batch 2: radioactive phosphorus (32P)

Empty protein shell

Phage DNA

Centrifuge

Centrifuge

Pellet

Pellet (bacterial cells and contents)

Radioactivity (phage protein) in liquid

Radioactivity (phage DNA) in pellet

Hershey + Chase (1952) T4 infection of E. coli

02_UnTable01.jpgChargaff (1949)

Rosalind FranklinWatson and Crick

1953: The double helix

Watson and Crick- 1953

Key aspects of the Watson-Crick model

- The 2 strands are in shape of a double helix-10.5 base pairs per turn of the helix

Hydrogen bond 3 end

5 end

3.4 nm

0.34 nm3 end

5 end(b) Partial chemical

structure(a) Key features of DNA structure

1 nm

Sugar–phosphate backbone

5 end

Nitrogenous bases

Thymine (T)

Adenine (A)

Cytosine (C)

Guanine (G)

DNA nucleotide

Sugar (deoxyribose) 3 end

Phosphate

Data used to deduce double helix:

1) Chemical structure of DNA polymer

2) Chargaff’s rules

3) Franklin’s X-ray diffraction data

(b) Franklin’s X-ray diffraction photograph of DNA

This told them:-2 anti-parallel DNA strands-Helical shape-Width, period of helix

Key aspects of the Watson-Crick model

-2 anti-parallel strands of DNA

-Sugar-phosphate backbone on outside, bases on inside

-Bases form pairs through hydrogen bonding

Hydrogen bond 3 end5 end

3.4 nm

0.34 nm3 end

5 end(b) Partial chemical

structure(a) Key features of DNA structure

1 nm

Cytosine (C)

Adenine (A) Thymine (T)

Guanine (G)

Base pairing

Purine Pyrimidine

Why A and C can’t base pair:

Fig. 16-UN1

Purine + purine: too wide

Pyrimidine + pyrimidine: too narrow

Purine + pyrimidine: width consistent with X-ray data

Watson and Crick- 1953

“It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

Fig. 16-9-2

A T

GC

T A

TA

G C

A T

GC

T A

TA

G C

(a) Parent molecule (b) Separation of strands

Fig. 16-9-3

A T

GC

T A

TA

G C

(a) Parent molecule

A T

GC

T A

TA

G C

(c) “Daughter” DNA molecules, each consisting of one parental strand and one new strand

(b) Separation of strands

A T

GC

T A

TA

G C

A T

GC

T A

TA

G C

Fig. 16-10

Parent cellFirst replication

Second replication

(a) Conservative model

(b) Semiconserva- tive model

(c) Dispersive model

Fig. 16-11a

EXPERIMENT

RESULTS

1

3

2

4

Bacteria cultured in medium containing 15N

Bacteria transferred to medium containing 14N

DNA sample centrifuged after 20 min (after first application)

DNA sample centrifuged after 20 min (after second replication)

Less dense

More dense

Fig. 16-11b

CONCLUSION

First replication Second replication

Conservative model

Semiconservative model

Dispersive model