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)

Chapter 2

Genes, Genetic Codes, and Mutation

DNA

Neucleotides{Phosphate

Deoxyribose sugar

Nitrogen base AdenineGuanineCytosineThymine

Purine

Pyrimidine

S

S

P

S

P

T

T

G

S

S

P

S

P

A

A

C

3‘

5‘

5‘

3‘

National Taiwan University Chau-Ti Ting

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

A

T

G

C

SW

R

Y

KM

B x

x D

Hx

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:UG:C

DNA replication: semiconservative replication

The polymerization processDNA polymerase 5' to 3'DNA polymerase acts at the replication forkLeading strand Lagging strand1. RNA oligonucleotides (primer) copied from DNA2. DNA polymerase elongates with new DNA Okazaki fragment3. DNA polymerase moves 5' RNA at the end of neighboring fragment and fills gap4. DNA ligase joins adjacent fragments

http://en.wikipedia.org/wiki/DNA_replication

Wikipedia Madprime

The nature of genes (Fig. 2-4)

Prokaryotesgene = regulatory region + coding region +

transcription termination signals

Eukaryotesgene = regulatory region + exons + introns +

transcription termination signals

National Taiwan University Chau-Ti Ting

Exon Exon Exon

Intron Intron

5’ 3’

Flanking region Flanking region

GC box

CAAT boxTATA box

Transcription initiation

Initiation codon

Stop codon

AATAAA box

Transcription termination

Poly(A) site

Promoter region

GT AG

Intron

19-27 bp upstream of the transcription startpoint

TACTAAC box

30 bp upstream of the 3’ end of the intron

GT-AG rule

5’ 3’

PseudogenesA 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 Li2000. Fundamentals of Molecular Evolution., p. 14. Sinauer Associates, Inc. Sunderland, MA, USA.

Wikipedia Dhorspool

Amino AcidsThe 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.

-NH2 (amine) group-COOH (carboxyl) groupside chain (-R group)

Source: Howard Hughes Medical Institutehttp://www.hhmi.org/genetictrail/glossary.html

ProteinsA 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 molecules.

Peptide two or more amino acids linked together

Residue each amino acid in a polypeptide

N terminus terminated with free amine group

C terminus terminated by a free carboxyl group

Source: Howard Hughes Medical Institutehttp://www.hhmi.org/genetictrail/glossary.html

Source: Howard Hughes Medical Institutehttp://www.hhmi.org/genetictrail/glossary.html

http://en.wikipedia.org/wiki/N-terminus

http://en.wikipedia.org/wiki/C-terminus

http://en.wikibooks.org/wiki/Structural_Biochemistry/Proteins/Structures

http://en.wikipedia.org/wiki/Public_domain

http://en.wikipedia.org/wiki/Public_domain

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.

ATA TGT ATA AAG GCA Ile Cys Ile Lys Ala

http://en.wikipedia.org/wiki/Stop_codon#cite_note-0

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) AGGCAAACCTACTGGTCTTAT original sequence(b) AGGCAAATCTACTGGTCTTAT C to T transition(c) AGGCAAACCTACTGCTCTTAT G to C transversion(d) AGGCAAACCTACTGCAAACAT recombination

GTCTT

ACCTA

(e) AGGCAACTGGTCTTAT deletion of ACCTA

(f) AGGCAAACCTACTAAAGCGGTCTTAT insertion of AAAGC

(g) AGGTTTGCCTACTGGTCTTAT inversion of GCAAAC

Source: Dan Graur and Wen-Hsiung Li2000. Fundamentals of Molecular Evolution., p. 26. Sinauer Associates, Inc. Sunderland, MA, USA.

Substitution mutations

Transition changes beween A and G, or between T and CTransversion changes between a purine and a pyrimidine

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.

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.

DNA CCG CTG CTCmRNA CCG CUG CUCAmino acid Proline Leucine Leucine

Source: Marjorie A. Hoy2003. Insect molecular genetics: an introduction to principles and applications, 2nd edition, p. 23. Academic Press. USA.

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.

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.

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 sequence of the encoded protein.

DNA CCG CTG CTCmRNA CCG CUG CUCAmino acid Proline Leucine Leucine

Addition or deletion (frameshift mutations) Deletion

Wild type UUG CUG AGG CCC GAG U….Deletion UUG CGA GGC CCG AGU ……

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.

(a) synonymousIle Cys Ile Lys Ala Leu Val Leu Leu ThrATA TGT ATA AAG GCA CTG GTC CTG TTA ACA

ATA TGT ATA AAG GCA CTG GTA CTG TTA ACAIle Cys Ile Lys Ala Leu Val Leu Leu Thr

(b) missenseIle Cys Ile Lys Ala Leu Val Leu Leu ThrATA TGT ATA AAG GCA CTG GTC CTG TTA ACA

ATA TGT ATA AAG GCA CTG TTA CTG TTA ACAIle Cys Ile Lys Ala Leu Phe Leu Leu Thr

(c) nonsense Ile Cys Ile Lys Ala Leu Val Leu Leu Thr

ATA TGT ATA AAG GCA CTG GTC CTG TTA ACA

ATA TGT ATA TAG GCACTGGTACTGTTAACAIle Cys Ile Stop Source: Dan Graur and Wen-Hsiung Li

2000. Fundamentals of Molecular Evolution., p. 27. Sinauer Associates, Inc. Sunderland, MA, USA.

RecombinationCrossing over (reciprocal recombination)Gene conversion (non-reciprocal recombination)

Deletions and insertionsmechanisms unequal crossing over

intrastrand deletionreplication slippage

indel = insertion-or-deletionframeshift mutation

Deletion

Wild type UUG CUG AGG CCC GAG U….Deletion UUG CGA GGC CCG AGU ……

Copyright DeclarationWork Licensing Author/Source Page

National Taiwan University Chau-Ti Ting

P3

National Institute of General Medical Sciences (NIGMS)http://images.nigms.nih.gov/index.cfm?event=viewDetail&imageID=25422012/02/24 visitedThis 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

National Taiwan University Chau-Ti Ting

P5

Wikipedia Madprimehttp://en.wikipedia.org/wiki/File:DNA_replication_split.svg2012/02/22 visited

P8

National Taiwan University Chau-Ti Ting

P10

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 Li2000. 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

24

Work Licensing Author/Source Page

Wikipedia Dhorspool http://en.wikipedia.org/wiki/File:Central_Dogma_of_Molecular_Biochemistry_with_Enzymes.jpg2012/02/22 visited

P12

P. 13. “The basic building blocks of proteins … linked together according to the genetic information encoded in DNA.”

Howard Hughes Medical Institutehttp://www.hhmi.org/genetictrail/glossary.html2012/02/22 visitedIt 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 Institutehttp://www.hhmi.org/genetictrail/glossary.html2012/02/22 visitedIt 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 Institutehttp://www.hhmi.org/genetictrail/glossary.html2012/02/22 visitedIt 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.png2012/02/22 visited

P15

Wikipedia LadyofHatshttp://en.wikipedia.org/wiki/File:Main_protein_structure_levels_en.svg2012/02/22 visited

P16

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 visitedIt is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright Act

P17

25

Work Licensing Author/Source Page

P. 17. “Genetic code: The set of correspondences between nucleotide pair triplets in DNA and amino acid in 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 visitedIt is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright Act .

P17

Dan Graur and Wen-Hsiung Li2000. 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 CTransversion changes between a purine and a pyrimidine”

Marjorie A. Hoy2003. Insect molecular genetics: an introduction to principles and applications, 2nd edition, p. 23. Academic Press. USA.http://books.google.com.tw/books?id=MPkwi-i33zYC&printsec=frontcover&hl=zh-TW#v=onepage&q&f=false2012/02/22 visitedIt is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright Act

P19

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 visitedIt 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 visitedIt is used subject to fair use doctrine in accordance with Articles 52 & 65 of Taiwan Copyright Act

P19,20

Dan Graur and Wen-Hsiung Li2000. 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