OUTLINE

1. DNA: The genetic material

2. Gene expression: The central dogma

3. Evolution: From genes to genomes,

from protein to proteomes

4. The hottest issues in molecular genetics

Lecture 1 2
Fields of Genetics

Lecture 1 3
Trait – skin color Phenotype: - black
- yellow
- white

Lecture 1 5
DNA history
 Griffith (1928) experimented on mice
and observed some harmless strains of
bacteria could change into harmful
strains. He called this transformation

 Avery (1944) discovered that DNA is the

nucleic acid that stores and transmits
the genetic information from one
generation to the next.

Lecture 1 6
Lecture 1 7
Lecture 1 8
More DNA history
 Hershey-Chase
(1952) concluded
that the genetic
material in bacteria
was DNA not
proteins

 Watson & Crick

(1953) – created
the double helix
model for DNA.
Lecture 1 9
Composition of DNA
 DNA is a polymer of nucleotides (‘building
block’) and a macromolecule
 Nucleotide consists of three components:
1. A phosphate group
2. A pentose sugar (Deoxyribose)
3. Nitrogenous bases:
- DNA: A, G, C, T
- RNA: A, G, C, U
 Sequence of bases encodes genetic traits

Lecture 1 10
Secondary structure of DNA

 Double helix structure consists of two

polynucleotide strands run in opposite
direction – antiparallel complementary
strands

 Two halves of the DNA molecule are

linked by hydrogen bonds between
nucleotide pair

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Lecture 1 15
Chargaff’s rules
(base-pairing rules)
 Chargaff discovered
how the nitrogenous
bases bond
together.
 He discovered that
Adenine always
bonds with Thymine
and that Cytosine
always bonds with
Guanine.

Lecture 1 16
OUTLINE

1. DNA: The genetic material

2. Gene expression: The central dogma

3. Evolution: From genes to genomes,

from protein to proteomes

4. The hottest issues in molecular genetics

Lecture 1 17
The central dogma of molecular
biology
 In 1958, Francis Crick introduced the
phrase ‘central dogma’ to represent the
flow of genetic information
 Crick chose the word ‘dogma’ thinking
that it meant ‘hypothesis’
 Actual meaning of ‘dogma’ is ‘a belief
that is to be accepted without doubt’

Lecture 1 18
The central dogma of molecular
biology

 The flow of information is

DNA  RNA protein
 Some viruses can use RNA as a template
for the synthesis of DNA in reverse
transcription.
 Many genes do not encode polypeptides;
their end-products are RNA molecules.

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(a) Major information pathways
(b) Special information pathways
Transcription and translation in
prokaryotes
 The primary
transcript is
equivalent to the
mRNA molecule.
 The mRNA codons
are translated into an
amino acid sequence
by the ribosomes.
 Codon is a sequence
of three nucleotides

Lecture 1 22
 Triplet Code

Lecture 1
23
Transcription and translation in
eukaryotes
 The primary transcript
(pre-mRNA) is a
precursor to the mRNA.
 The pre-mRNA is
modified at both ends,
and introns are
removed to produce the
mRNA.
 After processing, the
mRNA is exported to
the cytoplasm for
translation by
ribosomes.
 Introns (noncoding
sequences) vs Exons
(coding sequences)
Lecture 1 24
Excision of intron sequences

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Model organisms
 Geneticists focused their research on a
small number of species known as ‘model
organisms’ that are well suited for genetic
analysis
 A model organism is a species used in
experimental biology with the presumption
that what is learned from the analysis of
that species will hold true for other species,
especially other closely related species

Lecture 1 26
What features make a species suitable as a model
organism?
Key Points
 The central dogma of molecular biology
is that genetic information flows from
DNA to DNA during chromosome
replication, from DNA to RNA during
transcription, and from RNA to protein
during translation.
 DNA does not code for protein directly but
through RNA

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Key Points
 Transcription involves the synthesis of an
RNA transcript complementary to one
strand of DNA of a gene.

 Translation is the conversion of information

stored in the sequence of nucleotides in the
RNA transcript into the sequence of amino
acids in the polypeptide gene product,
according to the specifications of the
genetic code.
Lecture 1 29
OUTLINE

1. DNA: The genetic material

2. Gene expression: The central dogma

3. Evolution: From genes to genomes,

from protein to proteomes

4. The hottest issues in molecular genetics

Lecture 1 30
Lecture 1 31
Genomes
 Genome – total DNA in a single cell
 In eukaryotes, genome refers to all genes
present in one complete haploid set of
chromosomes
 Genomics – study of the DNA sequence,
organization, function & evolution of
genomes
 Look at all of the genes as a dynamic
system to determine how they interact &
influence biological pathways, networks,
physiology, and systems in a global sense

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Genomes
 By the end of 2013, the sequences of
almost 27,000 bacterial genomes, and
more than 6600 eukaryotic species
(including fungi, plants, and animals) had
been deciphered.
 Genomes of bacteria is very compact –
high density of genes relative to amount
of DNA
 Human genome – only 1.5% of the human
genome sequence codes for protein.

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Genome Comparisons

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Genomes
 The success of genomics has brought the
emergence of numerous ‘-omics’ sciences
(http://genomicglossaries.com/content/genomics_glossary.asp)
 Agricultural genomics
 Clinical genomics
 Industrial genomics
 Genome database:
 http://www.genomesize.com/
 http://www.cbs.dtu.dk/databases/DOGS/

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Online resources for genomics and model
organisms

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Proteomes
 Proteome is the complete set of proteins
encoded in the genome
 Proteome in an organism is variable both
temporally & between tissues according to
its physiology and the demands of a new
environment.

 Proteomics – study of the complement

of proteins to identify their localization,
functions, interactions

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Proteomes
 Less complex genomes – the number of
proteins approximately the same as the
number of genes.
 Yeast, worm, fruit fly.

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Proteomes
 More complex genomes – genes encode for
2 or more protein through alternative
splicing that produces different mRNAs
 Human: 1/3 or possibly 2/3 of human genes
undergo alternative splicing
 30,000-60,000 different genes within a
eukaryote’ genome, only a percentage of these
being expressed in a tissue
 15,000-20,000 genes are expressed in any cell,
& only a small number of differentially expressed
genes to form different tissue types

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Alternative Gene

1 2 3 4 5
Splicing

1 2 3 4 5

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41
Proteomes
 Families of related proteins had similarities
in their amino acid sequence
 New gene function is typically preceded by
the duplication of an already existing gene
 Followed by changes in nucleotide sequence
in one of the copies.

Ref. Genetics: Analysis of Genes & Genomes, 7th Ed

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OUTLINE

1. DNA: The genetic material

2. Gene expression: The central dogma

3. Evolution: From genes to genomes, from

protein to proteomes

4. The hottest issues in molecular

genetics
Lecture 1 43
 Pharmacogenomics
 Determine how drugs work in individual peoples
 Highly personalized medicine fits the unique
genetic makeup of each individual patient

 Stem cells
 The key to cure brain & spinal cord injuries, or
partly cure cancer
 Stem cells are pluripotent that can turn into any
kind of tissue
 Stem cell approach is at the center of
controversies due to the source of stem cells from
embryonic tissue

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 Aging
 Telomeres (the end of
chromosome) get too
short, cell dies & cell death
is clearly part of the aging
process
 Telomerase that can
prevent telomeres from
shortening seems a target
for anti-aging research, if
the geneticists can turn
telomerase on when it’s
wanted

 Proteomics
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 Bioinformatics = Molecular
biology + Computer
 Use computer to sort through
massive biological databases
 Provide gene-prediction software,
analytical tools to “mine the
data” from sequencing projects

 Gene chip (microarray)

 Determine quickly which genes
are at work (being expressed)
 Rapidly screen thousands of
genes to pick up on mutations
that causes diseases.
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 Genetics of infectious diseases
 Understand the genetic
background of highly virulent
diseases, for example bird flu, to
combat their effect

 Gene therapy
 To treat and cure diseases
caused by genetic disorders
 Introduce a healthy gene or shut
down an unwanted gene

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 Fitting new genes into plants and animals:
Genetically modified organism (GMO) or
Transgenic organism
 A GMO is one whose genome has been artificially
changed to carry foreign genes using
recombinant DNA methods

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 Octoploidy
strawberries

Triploid
seedless watermelon
52
 Cloning
 Make a copy of an
entire organism
 Big arguments for
and against cloning

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 DNA barcoding
 Use genetic code to
identify and track living
things
 Look for mtDNA-based
sequences unique to
particular species
 Nearly 65,000 species
matched with a DNA
barcode

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55
 Tra catfish
Pangasianodon hypophthalmus

Basa catfish
Pangasius bocourti
Background reading