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Introduction to Genetics

BIOL 2050
Tarushika Vasanthan, Phd

Chapter: 8
Nov 5th 2021
Lecture 6
Announcements

• Test 1 grades will be posted next week

• Quiz 2: November 19th 2021


• Covers lectures 6 and 7

• Test 2: Saturday December 11th 2021, @ 11:00 AM – 1:00 PM [Lectures post reading week]

• If accommodations are needed, please early register with CAT


Lecture 6

DNA & RNA Structure


CHAPTER 8: Learning Objectives

By the end of this lecture, students will be able to:

• List key characteristics of genetic material

• Describe how researchers identified DNA as the source of genetic information

• Outline the primary and secondary structures of DNA

• Explain how large amounts of DNA are packed into a cell.

• Describe the special features of telomeres.


Chapter 8.1

The Genetic Material Possesses Several Key Characteristics

• Genetic material must contain complex information.

• Genetic material must replicate faithfully.

• Genetic material must encode the phenotype.

• Genetic material must have the capacity to vary.


Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Establishing DNA as the Hereditary Molecule:


• Frederick Meischer was interested in the composition of the nucleus
• Extracted unknown acidic substance from the pus of patients  He names this substances “nuclein”
Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Establishing DNA as the Hereditary Molecule:


• Edwards Chargraff did NOT agree that all 4 nitrogen bases were in equal amounts
• Found – bases always occur in definite ratios
• A and T were matched
• G and C were matched

Base Composition (percentage*) Ratio Ratio Ratio


Source of DNA A T G C A/T G/C (A + G)/ (T + C)
E. coli 26.0 23.9 24.9 25.2 1.09 0.99 1.04
Yeast 31.3 32.9 18.7 17.1 0.95 1.09 1.00
Sea urchin 32.8 32.1 17.7 18.4 1.02 0.96 1.00
Rat 28.6 28.4 21.4 21.5 1.01 1.00 1.00
Human 30.3 30.3 19.5 19.9 1.00 0.98 0.99
Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Establishing DNA as the Hereditary Molecule:


• Meischer’s nuclein was still unknown – a pneumonia epidemic hit near the end of WWII
• This led Frederick Griffith to accidently find the function of DNA in inheritance
• He used 2 strains:
• One had a capsule that surrounded each cell (looked smooth and glossy)  Smooth strain; S-strain
• The other lacked a capsule forming rough and irregular colonies when cultured  R-strain
Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA


Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Establishing DNA as the Hereditary Molecule:


Avery, McLeod, and McCarty: DNA Transformation Confirmed
• Oswald Avery, Colin McLeod, and Maclyn McCarty grew different strains of streptococcus bacteria
• The strains were isolated and contained the S and R strain
• They wanted to know which part of the S-strain bacteria cell was responsible for making R-strain bacteria virulent?
• Possibilities: DNA, RNA, and proteins
Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA


Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Hershey and Chase: DNA is the Hereditary Material

• Alfred Hershey and Martha Chase wanted to determine whether proteins or DNA was the genetic material
• They used virus and E.coli
• Virus they used was bacteriophages – a virus that infects bacteria; contains DNA + protein coat
• Bacteriophage inserts its genetic material into the bacterium and uses the bacteria’s cellular process to produce more
bacteriophages
Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA


Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Hershey and Chase: DNA is the Hereditary Material


• Hershey and Chase knew – bacteria can be transformed by virus BUT did not know which part of the virus did this
• Used radioisotopes to label molecules – specifically radioisotope of phosphorous and sulfur
• Sulfur was used to label proteins because protein contain sulfur but not DNA
• Phosphorus was used to label DNA
Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA


Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Wilkins and Franklin: Another Piece of the Puzzle


Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA


Chapter 8.2

All Genetic Information Is Encoded in the Structure of DNA or RNA

Watson and Crick: Building a Model of DNA

• James Watson and Francis Crick built a model based on


everything they knew about DNA:
• 4 different nitrogen bases
• Chargaff’s ratios of the bases
• Phosphate and sugar backbones
• Double Helix and inward facing bases

1953, published article on DNA model


1962, Nobel Prize to Watson, Crick & Wilkins
1968, Watson published book "The Double Helix"
Chapter 8.3

Fig. 8.7: Sugar component in DNA versus RNA

Purine (double ring) bases Pyrimidine (single ring) bases


Chapter 8.3
Chapter 8.3

Although RNAs are usually found as single-stranded


molecules in the cell (Fig. 8.11; on left) – they can also
5' end
form double-stranded molecules (Fig. 10.1b; below)

In RNA:
G – C (3 H-bonds)
A – U (2 H-bonds)
3' end
Chapter 8.3

Complementary basepairing can occur between:


DNA:DNA RNA:RNA DNA:RNA
5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’

G C G C G C G C
T A U A T A U A
C G C G C G C G
T A U A T A U A
A T A U A U A T
A T A U A U A T

3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’

Hybridization can also occur between single-stranded nucleic


acids as long as they share a region that can complementary
base-pair
Chapter 8.3

Different forms of DNA helix


A form
• Right–handed helix
• Less H2O present
• Shorter and wider than B-form
B form
• Right–handed helix
• Lots of H2O present
• Most stable physiologically

Z form
• Left–handed helix
• Zigzag sugar-phosphate backbone
• Stretches of DNA sequences (i.e.
CGCGCG…
Chapter 8.4

How do compact genomic DNA into small space


This is a problem in prokaryotes and eukaryotes
Chapter 8.4

Bacterial genomic DNA is contained in a single double-stranded and closed circular


chromosome

The bacterial chromosome is organized and compacted into loops by specialized


proteins within the bacterial cell

Although there is
no nucleus in a
bacterial cell – the
DNA is localized in
a distinct clump
within the
cytoplasm
Chapter 8.4

Genomic DNA in eukaryotes are associated with histones to form chromatin in the nucleus
Each nucleosome 1st level of chromatin
consists of two organization:
molecules of each type
of CORE HISTONE:
H2A, H2B, H3 and H4 H1 LINKER
HISTONE
Core histones are small and
highly basic proteins +ve
(Arg and Lys rich) –> helps
maintain strong contact with
–ve DNA

2nd level of chromatin


organization:
Chapter 8.4

Different levels of DNA organization and compaction in eukaryotes


Chapter 8.4

Epigenetic Changes Associated with Chromatin Modifications

Underlying DNA at this locus is identical in all


mice shown – differences in resulting coat
colour is due to differences in DNA
methylation
Chapter 8.4

Epigenetic Changes Associated with Chromatin Modifications


Chapter 8.5

Telomeres

• Telomeres appear like small dots at the end of chromosomes- they cap of the ends of the chromosomes
• Important – as it protects the DNA from losing valuable coding information during replication
• They have several functions:
Chapter 8.5

Telomeres
Central Dogma – the flow of genetic information

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