Chapter 2
Genes, Genetic Codes, and Mutation
Chau-Ti Ting
ctting@ntu.edu.tw
Unless noted, the course materials are licensed under Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 Taiwan (CC
BY-NC-SA 3.0)
DNA
Neucleotides
{
Phosphate
Deoxyribose sugar
Nitrogen base
Adenine
Guanine
Cytosine
Thymine
Purine
Pyrimidine
5‘
S
A
S
S
G
C
P
S
S
T
A
P
P
3‘
P
T
S
5‘
National Taiwan University Chau-Ti Ting
3‘
Source: National Institute of General Medical Sciences (NIGMS)
http://images.nigms.nih.gov/index.cfm?event=viewDetail&imageID=2542
One-letter abbreviations for the DNA alphabet
B
x
H
A
M
x
D
C
G
R
W
S
Y
x
K
T
x
V
National Taiwan University Chau-Ti Ting
RNA
Single-stranded nucleotides
Ribose sugar in its nucleotides, rather than deoxyribose
Four nitrogenous bases: A, C, G, U (uracil)
A:U
G:C
DNA replication: semiconservative replication
The polymerization process
DNA polymerase
5' to 3'
DNA polymerase acts at the replication fork
Leading strand
Lagging strand
1. RNA oligonucleotides (primer) copied from DNA
2. DNA polymerase elongates with new DNA  Okazaki
fragment
3. DNA polymerase moves 5' RNA at the end of neighboring
fragment and fills gap
4. DNA ligase joins adjacent fragments
http://en.wikipedia.org/wiki/DNA_replication
Wikipedia Madprime
The nature of genes
(Fig. 2-4)
Prokaryotes
gene = regulatory region + coding region +
transcription termination signals
Eukaryotes
gene = regulatory region + exons + introns +
transcription termination signals
Intron
Intron
Flanking region
Flanking region
5’
Initiation
codon
GC box
CAAT box
TATA box
19-27 bp upstream
of the transcription
startpoint
Exon
Exon
Exon
Stop
codon
Transcription
initiation
AATAAA box
Poly(A) site
30 bp upstream
of the 3’ end of
the intron
Intron
5’
Transcription
termination
TACTAAC box
Promoter region
GT
National Taiwan University Chau-Ti Ting
3’
3’
AG
GT-AG rule
Pseudogenes
A pseudogene is a nongenic DNA segment that exhibits
a high degree of similarity to a functional gene but which
contains defects, such as nonsense and frameshift mutations,
that prevent it from being expressed properly.
Source: Dan Graur and Wen-Hsiung Li
2000. Fundamentals of Molecular Evolution., p. 14. Sinauer Associates, Inc. Sunderland, MA, USA.
Wikipedia Dhorspool
Amino Acids
The basic building blocks of proteins. There are 20
different amino acid types. Each protein consists of a
different sequence of amino acids linked together according
to the genetic information encoded in DNA.
Source: Howard Hughes Medical Institute
-NH2 (amine) group
http://www.hhmi.org/genetictrail/glossary.html
-COOH (carboxyl) group
side chain (-R group)
Proteins
A molecule composed of amino acids linked together in a
particular order specified by a gene's DNA sequence. Proteins
perform a wide variety of functions in the cell; these include
serving as enzymes, structural components, or signaling
Source: Howard Hughes Medical Institute
molecules.
http://www.hhmi.org/genetictrail/glossary.html
Peptide
Residue
two or more amino acids linked together
Source: Howard Hughes Medical Institute
http://www.hhmi.org/genetictrail/glossary.html
each amino acid in a polypeptide
http://en.wikibooks.org/wiki/Structural_Biochemistry/Proteins/Structures
N terminus
terminated with free amine group
http://en.wikipedia.org/wiki/N-terminus
C terminus
terminated by a free carboxyl group
http://en.wikipedia.org/wiki/C-terminus
Genetic Code
• Codon: a section of DNA (3 nucleotide pairs in length) that
encodes a single amino acid.
• Genetic code: The set of correspondences between nucleotide
pair triplets in DNA and amino acid in protein.
• Stop codons (termination codons) can be recognized by
release factors.
http://en.wikipedia.org/wiki/Stop_codon#cite_note-0
ATA TGT ATA AAG GCA
Ile Cys Ile
Lys Ala
Source: A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and W. M. Gelbart.
2000. An Introduction to Genetic Analysis, 7th edition. W. H. Freeman and Company. New York, USA.
http://www.ncbi.nlm.nih.gov/books/NBK21878/
(a)
(b)
(c)
(d)
AGGCAAACCTACTGGTCTTAT
AGGCAAATCTACTGGTCTTAT
AGGCAAACCTACTGCTCTTAT
AGGCAAACCTACTGCAAACAT
original sequence
C to T transition
G to C transversion
recombination
GTCTT
ACCTA
(e) AGGCAACTGGTCTTAT
deletion of ACCTA
(f) AGGCAAACCTACTAAAGCGGTCTTAT
insertion of AAAGC
(g) AGGTTTGCCTACTGGTCTTAT
inversion of GCAAAC
Source: Dan Graur and Wen-Hsiung Li
2000. Fundamentals of Molecular Evolution., p. 26. Sinauer Associates, Inc. Sunderland, MA, USA.
Substitution mutations
Transition
Transversion
changes beween A and G, or between T and C
changes between a purine and a pyrimidine
Source: Marjorie A. Hoy
2003. Insect molecular genetics: an introduction to principles and applications, 2nd edition, p. 23. Academic Press. USA.
Synonymous (silent mutations)
Nucleotide changes in the encoding part of a gene that do not
result in a change in the amino acid sequence of the encoded protein.
Source: A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and W. M. Gelbart.
2000. An Introduction to Genetic Analysis, 7th edition. W. H. Freeman and Company. New York, USA.
Nonsynonymous (replacement mutations)
Nucleotide changes in the encoding part of a gene that result in
a change in the amino acid sequence of the encoded protein.
Source: A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and W. M. Gelbart.
2000. An Introduction to Genetic Analysis, 7th edition. W. H. Freeman and Company. New York, USA.
DNA
mRNA
Amino acid
CCG
CCG
Proline
CTG
CUG
Leucine
CTC
CUC
Leucine
Types of Mutation
Nucleotide substitution
Replacement mutations: Nucleotide changes in the
encoding part of a gene that result in a change in the amino acid
sequence of the encoded protein.
Silent mutations: Nucleotide changes in the encoding part
of a gene that do not result in a change in the amino acid
Source: A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and
sequence of the encoded protein.
W. M. Gelbart.
2000. An Introduction to Genetic Analysis, 7th edition. W. H. Freeman and
Company. New York, USA.
DNA
CCG
CTG
CTC
mRNA
CCG
CUG
CUC
Amino acid Proline Leucine Leucine
Addition or deletion (frameshift mutations)
Deletion

Wild type UUG CUG AGG CCC GAG U….
Deletion UUG CGA GGC CCG AGU ……
(a) synonymous
Ile
Cys
Ile
ATA TGT ATA
Lys
AAG
Ala
GCA
Leu
CTG
ATA
Ile
Val
GTC

GTA
Val
Leu
CTG
Leu
TTA
Thr
ACA
CTG
Leu
TTA
Leu
ACA
Thr
Leu
CTG
Leu
TTA
Thr
ACA
CTG
Leu
TTA
Leu
ACA
Thr
Leu
CTG
Leu
TTA
Thr
ACA
TGT
Cys
ATA
Ile
AAG
Lys
GCA
Ala
CTG
Leu
(b) missense
Ile
Cys
ATA TGT
Ile
ATA
Lys
AAG
Ala
GCA
Leu
CTG
ATA
Ile
TGT
Cys
ATA
Ile
AAG
Lys
GCA
Ala
CTG
Leu
Val
GTC

TTA
Phe
(c) nonsense
Ile
Cys
ATA TGT
Ile
ATA
Ala
GCA
Leu
CTG
Val
GTC
ATA
Ile
ATA
Ile
Lys
AAG

TAG
Stop
TGT
Cys
GCACTGGTACTGTTAACA
Source: Dan Graur and Wen-Hsiung Li
2000. Fundamentals of Molecular Evolution., p. 27. Sinauer Associates, Inc. Sunderland, MA, USA.
Recombination
Crossing over (reciprocal recombination)
Gene conversion (non-reciprocal recombination)
Deletions and insertions
mechanisms unequal crossing over
intrastrand deletion
replication slippage
indel = insertion-or-deletion
frameshift mutation
Deletion

Wild type
UUG CUG AGG CCC GAG U….
Deletion
UUG CGA GGC CCG AGU ……
Copyright Declaration
Work
Licensing
Author/Source
Page
P3
National Taiwan University Chau-Ti Ting
National Institute of General Medical Sciences (NIGMS)
http://images.nigms.nih.gov/index.cfm?event=viewDetail&imageID=2542
2012/02/24 visited
This work is used subject to the fair use doctrine of :
•Article 46, 52 & 65 Taiwan Copyright Act.
•Permission for Use NIGMS Image Gallery http://images.nigms.nih.gov/
P4
P5
National Taiwan University Chau-Ti Ting
P8
Wikipedia Madprime
http://en.wikipedia.org/wiki/File:DNA_replication_split.svg
2012/02/22 visited
P10
National Taiwan University Chau-Ti Ting
P. 11. “A pseudogene is
a nongenic DNA
segment that exhibits a
high degree of … that
prevent it from being
expressed properly.”
Dan Graur and Wen-Hsiung Li
2000. Fundamentals of Molecular Evolution., p. 14. Sinauer Associates, Inc.
Sunderland, MA, USA.
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan
Copyright Act
P11
Work
Licensing
Author/Source
Page
Wikipedia Dhorspool
http://en.wikipedia.org/wiki/File:Central_Dogma_of_Molecular_Biochemistry_with_Enz
ymes.jpg
2012/02/22 visited
P12
P. 13. “The basic building
blocks of proteins … linked
together according to the
genetic information encoded
in DNA.”
Howard Hughes Medical Institute
http://www.hhmi.org/genetictrail/glossary.html
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan
Copyright Act and copyright notice of HHMI
(http://www.hhmi.org/popups/copyright.html)
P13
P. 14. “A molecule
composed of amino acids
linked together in …
structural components, or
signaling molecules.”
Howard Hughes Medical Institute
http://www.hhmi.org/genetictrail/glossary.html
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan
Copyright Act and copyright notice of HHMI
(http://www.hhmi.org/popups/copyright.html)
P14
P. 14. “Peptide two or more
amino acids linked together”
Howard Hughes Medical Institute
http://www.hhmi.org/genetictrail/glossary.html
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan
Copyright Act and copyright notice of HHMI
(http://www.hhmi.org/popups/copyright.html)
P14
Wikipedia National Human Genome Research Institute (NHGRI)
http://en.wikipedia.org/wiki/File:Protein-primary-structure.png
2012/02/22 visited
Wikipedia LadyofHats
http://en.wikipedia.org/wiki/File:Main_protein_structure_levels_en.svg
2012/02/22 visited
P. 17. “Codon: a section of
DNA (3 nucleotide pairs in
length) that encodes a single
amino acid.”
A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and W. M. Gelbart.
2000. An Introduction to Genetic Analysis, 7th edition. W. H. Freeman and Company.
New York, USA.
http://www.ncbi.nlm.nih.gov/books/NBK21878/
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan
Copyright Act
P15
P16
P17
24
Work
P. 17. “Genetic code: The set
of correspondences between
nucleotide pair triplets in
DNA and amino acid in
protein.”
Licensing
Author/Source
Page
A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and W. M. Gelbart.
2000. An Introduction to Genetic Analysis. 7th edition. W. H. Freeman and Company. New
York, USA.
http://www.ncbi.nlm.nih.gov/books/NBK21878/
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright
Act .
P17
Dan Graur and Wen-Hsiung Li
2000. Fundamentals of Molecular Evolution., p. 26. Sinauer Associates, Inc. Sunderland, MA,
USA.
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright
Act
P18
P. 19. “Transition changes
beween A and G, or between
T and C
Transversion changes
between a purine and a
pyrimidine”
P19
Marjorie A. Hoy
2003. Insect molecular genetics: an introduction to principles and applications, 2 nd edition, p. 23.
Academic Press. USA.
http://books.google.com.tw/books?id=MPkwi-i33zYC&printsec=frontcover&hl=zhTW#v=onepage&q&f=false
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright
Act
P. 19, 20. “Nucleotide
changes in the encoding part
of a gene that do not result in
a change in the amino acid
sequence of the encoded
protein.”
A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and W. M. Gelbart.
2000. An Introduction to Genetic Analysis, 7th edition. W. H. Freeman and Company. New
York, USA.
http://www.ncbi.nlm.nih.gov/books/NBK21878/
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright
Act
P19,20
P. 19, 20. “Nucleotide
changes in the encoding part
of a gene that result in a
change in the amino acid
sequence of the encoded
protein.”
A. J. F. Griffiths, J. H. Miller, D. T. Suzuki, R. C. Lewontin, and W. M. Gelbart.
2000. An Introduction to Genetic Analysis, 7th edition. W. H. Freeman and Company. New
York, USA.
http://www.ncbi.nlm.nih.gov/books/NBK21878/
2012/02/22 visited
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright
Act
P19,20
Dan Graur and Wen-Hsiung Li
2000. Fundamentals of Molecular Evolution., p. 27. Sinauer Associates, Inc. Sunderland, MA,
USA.
It is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright
Act
P21
25