SCIE 1120 Chemistry and Life

DNA: The molecule of heredity

Prof. Guang ZHU

Division of Life Science

Email: gzhu@ust.hk
Phone: 8705
Apr.17, 2025, 3:00-4:20pm
LT-J
Cells are Building Blocks of Living Organisms

4 days

4 months

1year

Lung Cell: 17 months

Skin cell:three weeks
 The Molecules of Life

• All living things are made up of

four classes of large biological
molecules: carbohydrates,
lipids, proteins, and nucleic
acids
Lipid
• Macromolecules are large
molecules composed of
thousands of covalently
connected atoms
• Molecular structure and
function are inseparable

Facts Of Evolution: The Molecules Of Life https://www.youtube.com/watch?v=nvJFI3ChOUU

Macromolecules are polymers, built from monomers

◼ A polymer is a long molecule consisting of many similar

building blocks
◼ These small building-block molecules are called monomers
◼ Three of the four classes of life’s organic molecules are
polymers
◼ Carbohydrates
◼ Proteins
◼ Nucleic acids
 Macromolecules are polymers built from monomers
A polymer is a long molecule
(a) Dehydration reaction: synthesizing a polymer
◼
1 2 3
Short polymer Unlinked monomer
consisting of many similar building
Dehydration removes
blocks
a water molecule,
forming a new bond. ◼ These small building-block molecules
are called monomers
1 2 3 4
◼ Three of the four classes of life’s
Longer polymer
organic molecules are polymers
(b) Hydrolysis: breaking down a polymer
◼ Carbohydrates
1 2 3 4
◼ Proteins

◼ Nucleic acids
Hydrolysis adds
a water molecule,
breaking a bond.

1 2 3
The Diversity of Polymers
◼ Each cell has thousands of different macromolecules
◼ Macromolecules vary among cells of an organism, vary more within a
species, and vary even more between species
◼ An immense variety of polymers can be built from a small set of
monomers
examples:
a protein of 100 amino acids can have 20100
possible linear arrangements.
a DNA of 50 nucleotides can have 450 possible linear
arrangements. (computer code is binary (232 or 264 ) )
 DNA: The molecule of heredity

Central dogma

reverse
transcription
(RNA->DNA)
Reverse
Transcriptase

RNA replicase
(RNA->RNA)

In eukaryotic cells, genetic instructions are housed in the nucleus

 • A full-grown person consisting 100 trillion
(100x1012) cells from a single fertilized egg cell.
During each cell division the genetic material
has to be copied exactly.
Fertilized egg cell • During the development of a human, there are
at least trillion numbers of cell divisions, any
mistake could be fatal.
Cardiovascular System
• Eventually, replication defect kicks in. This could
Yamanaka factor ultimately relate to diseases and aging
• During animal development, many cells become
more specialized, the cellular differentiation
which requires many different proteins. But their
genome remain same.

100 trillion cells

 DNA organization in eukaryotic cells

Chromosomes in a human somatic cell (3 meters long)

(cells of a living organism other than the stem, sperm and egg cells)
Total:67 billion miles long—the same as about 150,000 round trips to the Moon
Dogs have 78 chromosomes; chimpanzee has 48 chromosomes
 DNA organization

Chromatid

DNA could store all of the world's data in one room

1.8 bits of data per nucleotide due to errors
 Basic definitions
•A gene is a sequence of DNA that encodes
for a specific trait (traits may also be
influenced by multiple genes) (20K genes in
human)
•The position of a gene on a particular
chromosome is called the locus (plural = loci)
•An allele is a variant form of a gene (such as
eye color). Humans are called diploid
(ploidy=#chromosomes) organisms because
CRISPR/Cas9 editing technology they have two alleles at each genetic locus,
with one allele inherited from each parent.

Homologous chromosomes are made up of

chromosome pairs of approximately the
same length, centromere position, and
staining pattern, for genes with the same
corresponding loci. One homologous
chromosome is inherited from the organism's
mother; the other is inherited from the
organism's father.
HER2 gene in chromosome 17
◼ HER2 (human epidermal growth factor receptor 2) is a
gene that can play a role in the development of breast
cancer (proliferation). Pathology report should include
information about HER2 status. In about 10% to 20% of
breast cancers, the HER2 gene doesn't work correctly and
makes too many copies of itself. All these
extra HER2 genes tell breast cells to make too many HER2
receptors (HER2 protein overexpression) Angelina Jolie
◼ Genes contain the recipes for the various proteins for a cell
needs to stay healthy and function normally. Some genes
and the proteins they make can influence how a breast
cancer behaves and how it might respond to a specific
treatment. Cancer cells from a tissue sample can be tested
to see which genes are normal and abnormal. The
proteins they make can also be tested.
Life’s Operating Instructions
◼ In 1953, James Watson and Francis Crick introduced an
elegant double-helical model for the structure of
deoxyribonucleic acid, or DNA
◼ DNA, the substance of inheritance, is the most celebrated
molecule of our time
◼ physiological hereditary information is encoded in DNA and
reproduced in all cells of the body
◼ This DNA program directs the development of biochemical,
anatomical, physiological, and (to some extent) behavioral
characters (characters, including selfishness)
Structure of Double Helix DNA by X-ray Crystallography
X-ray crystallography
Diffracted
X-rays

X-ray
source X-ray
beam

Crystal Digital detector X-ray diffraction

pattern
RESULTS
RNA DNA

RNA
polymerase II
 DNA is the genetic material
◼ In 1928 Griffith worked with two strains
EXPERIMENT
of a bacterium (a subtype of a biological
Mixture of
Living S cells Living R cells
Heat-killed
S cells
heat-killed species), one pathogenic and one
S cells and
(control) (control) (control) living R cells harmless
◼ When he mixed heat-killed (60oC)
remains of the pathogenic strain with
living cells of the harmless strain, some
living cells became pathogenic. He called
this phenomenon transformation
RESULTS
(something is transferred from S to R).
Mouse dies Mouse healthy Mouse healthy Mouse dies ◼ Their conclusion was based on
experimental evidence that only DNA
Pneumonia Living S cells
worked in transforming harmless bacteria
into pathogenic bacteria and was not well
accepted at that time.
 1 Attachment

Virus and infection

2 Entry of phage
DNA and
Membranous degradation
RNA Capsomere RNA of host DNA
envelope
DNA Capsid 5 Release
DNA
Head
Tail Phage assembly
Capsomere
sheath
of capsid
Tail
fiber
Glycoprotein Glycoproteins

18  250 nm 70–90 nm (diameter) 80–200 nm (diameter) 80  225 nm

4 Assembly
3 Synthesis of
Head Tail Tail viral genomes
fibers and proteins

20 nm 50 nm 50 nm 50 nm
(a)Tobacco (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4
mosaic virus
Evidence That Viral DNA, not Protein, Can
Program Cells
◼ Viruses, called bacteriophages, are widely used in
molecular genetics research
◼ (1) Grow the infected bacteria in 35S solution to label
proteins and purify the virus, (2) after ejecting of DNA
into new bacteria and centrifugation, the soluble
portion gives out detectable radiation produced by 36S
incorporating proteins of virus, while bacteria
containing pellet does not.
◼ (1) Grow the infected bacteria in 32P solution to label
nucleic acids of virus, (2) after ejecting of DNA into
new bacteria and centrifugation of the pellet portion
containing phage DNA gives out detectable radiation
produced by 32P labeled DNA ,while soluble port
containing no radiation

<30mins
32P and 36S in DNA and Protein
Amino acids nucleotides
 Building a Structural Model of DNA and RNA
Structures of DNA and RNA

Rosalind Franklin Franklin’s X-ray diffraction A-DNA B-DNA Z-DNA G-quadruplex DNA
photograph of DNA 11bp 10bp 12bp 4Gs
RH RH LF

◼ Maurice Wilkins and Rosalind Franklin were using a technique

called X-ray crystallography to study molecular structure
◼ Franklin produced a picture of the DNA molecule using this
technique

tRNA mRNA Protein/DNA complex

 Nucleic acids store, transmit, and help express
hereditary information
DNA ◼ The amino acid sequence of a polypeptide is programmed
by a unit of inheritance called a gene (A gene is a
segment of DNA that encodes function→ a protein)
1 Synthesis of
mRNA mRNA ◼ Genes are made of DNA, a nucleic acid made of
monomers called nucleotides
◼ There are two types of nucleic acids
NUCLEUS
CYTOPLASM ◼ Deoxyribonucleic acid (DNA)
mRNA
◼ Ribonucleic acid (RNA)
2 Movement of ◼ DNA provides directions for its own replication
mRNA into Ribosome
cytoplasm ◼ DNA directs synthesis of messenger RNA (mRNA) and,
3 Synthesis
through mRNA, controls protein synthesis
of protein ◼ Protein synthesis occurs on ribosomes

Amino
Polypeptide acids
DNA RNA Protein
 The Components of Nucleic Acids
Sugar-phosphate backbone
5 end Nitrogenous bases
Pyrimidines
5C

3C

Nucleoside ◼ Nucleic acids are polymers called polynucleotides

Nitrogenous
Cytosine (C) Thymine (T, in DNA)Uracil (U, in RNA)
◼ Each polynucleotide is made of monomers called
base
nucleotides
5C Purines ◼ Each nucleotide consists of a nitrogenous base, a
pentose sugar, and one or more phosphate
1C groups
Phosphate 3C
5C group Sugar ◼ The portion of a nucleotide without the phosphate
group is called a nucleoside
(pentose)
Adenine (A) Guanine (G)
3C (b) Nucleotide
◼ Nucleoside = nitrogenous base + sugar
Sugars
3 end
◼ There are two families of nitrogenous bases
(a) Polynucleotide, or nucleic acid
◼ Pyrimidines (cytosine, thymine, and uracil)
have a single six-membered ring
Deoxyribose (in DNA) Ribose (in RNA) ◼ Purines (adenine and guanine) have a six-
(c) Nucleoside components
membered ring fused to a five-membered ring
◼ In DNA, the sugar is deoxyribose (ATGC) ; in RNA,
the sugar is ribose (AUGC)
◼ Nucleotide = nucleoside + phosphate group
 Nucleotide Polymers (Facts)
◼ Nucleotides are linked together to build a polynucleotide
◼ Adjacent nucleotides are joined by covalent bonds that form between the —OH group on the 3 carbon of one
nucleotide and the phosphate on the 5 carbon on the next
◼ These links create a backbone of sugar-phosphate units with nitrogenous bases as appendages
◼ The sequence of bases along a DNA or mRNA polymer is unique for each gene
◼ RNA molecules usually exist as single polynucleotide chains
◼ DNA molecules have two polynucleotides spiraling around an imaginary axis, forming a double helix
◼ In the DNA double helix, the two backbones run in opposite 5→ 3 directions (positive direction) from each
other, an arrangement referred to as antiparallel
◼ One DNA molecule includes many genes
◼ The nitrogenous bases in DNA pair up and form hydrogen bonds: adenine (A) always with thymine (T), and guanine
(G) always with cytosine (C) Called complementary (A-T, G-C) base pairing
◼ Complementary pairing can also occur between two RNA molecules or between parts of the same molecule
◼ In RNA, thymine is replaced by uracil (U) so A and U pair (A-U, G-C)
 Additional Features
5 end
C G
C G Hydrogen bond
3 end
G C
G C T A
3.4 nm
T A
G C G C
Chargaff’s rules
C G
• The base composition of DNA varies
A T
1 nm C G between species
C G
T A
• In any species the number of A and T
C G
G C
A T
bases are equal, and the number of G
and C bases are equal
A T 3 end
A T 0.34 nm 5 end
T A
The basis for these rules was not understood
(a)Key features of (b) Partial chemical structure (c)Space-filling
DNA structure model until the discovery of the double helix
AT pair has two hydrogen bonds, while CG pair has three H-
bond. More H-bonds → higher melting temperatures (more
stable) (50-90 C)
 Interesting facts
How can shrimps survive in water 4 times Arsenic-DNA
hotter than boiling point?

Mono Lake, California

The newly discovered microbe, strain GFAJ-1, is a

member of a common group of bacteria, the
Gammaproteobacteria. In the laboratory, the researchers
successfully grew microbes from the lake on a diet that
was very lean on phosphorus but included generous
helpings of arsenic. When researchers removed the
phosphorus and replaced it with arsenic the microbes
Thousands of the newly discovered species of shrimp. Shrimp continued to grow. Subsequent analyses indicated that the
mass around an oceanic hydrothermal vent beneath the arsenic was being used to produce the building blocks of
Cayman Islands (5000m), in temperatures in excess of new GFAJ-1 cells.(Science 2010)
450C (Nat. Commu., 10 January 2012)