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How an Organism’s Genotype Determines Its Phenotype
• An organism’s genotype is its genetic makeup, the
sequence of nucleotide bases in DNA.
• The phenotype is the organism’s physical traits,
which arise from the actions of a wide variety of
proteins.
© 2013 Pearson Education, Inc.
29
• DNA specifies the synthesis of proteins in two
stages:
1. transcription, the transfer of genetic information from DNA into an RNA molecule and
2. translation, the transfer of information from RNA into a protein.
How an Organism’s Genotype Determines Its Phenotype
© 2013 Pearson Education, Inc.
30
© 2013 Pearson Education, Inc.
Bioflix Animation: Protein Synthesis
31 Figure 10.8-1
DNA
Cytoplasm
Nucleus
32
Figure 10.8-2
DNA
Cytoplasm
NucleusRNA
TRANSCRIPTION
33 Figure 10.8-3
DNA
Cytoplasm
NucleusRNA
Protein
TRANSCRIPTION
TRANSLATION
34
• The major breakthrough in demonstrating the
relationship between genes and enzymes came in
the 1940s from the work of American geneticists
George Beadle and Edward Tatum with the bread
mold Neurospora crassa.
How an Organism’s Genotype Determines Its Phenotype
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• Beadle and Tatum
– studied strains of mold that were unable to grow on the usual growth medium,
– determined that these strains lacked an enzyme in a metabolic pathway that synthesized arginine,
– showed that each mutant was defective in a single gene, and
– hypothesized that the function of an individual gene is to dictate the production of a specific enzyme.
How an Organism’s Genotype Determines Its Phenotype
© 2013 Pearson Education, Inc.
36
Figure 10.9 37
• The one gene–one enzyme hypothesis has since
been modified.
• The function of a gene is to dictate the production
of a polypeptide.
• A protein may consist of two or more different
polypeptides.
How an Organism’s Genotype Determines Its Phenotype
© 2013 Pearson Education, Inc.
38
From Nucleotides to Amino Acids: An Overview
• Genetic information in DNA is
– transcribed into RNA, then
– translated into polypeptides,
– which then fold into proteins.
© 2013 Pearson Education, Inc.
39
• What is the language of nucleic acids?
– In DNA, it is the linear sequence of nucleotide bases.
– A typical gene consists of thousands of nucleotides in a specific sequence.
• When a segment of DNA is transcribed, the result
is an RNA molecule.
• RNA is then translated into a sequence of amino
acids in a polypeptide.
From Nucleotides to Amino Acids: An Overview
© 2013 Pearson Education, Inc.
40
Figure 10.10
Amino acid
RNA
TRANSCRIPTION
DNA strand
Polypeptide
Codon
Gene 1
Gene 3
Gene 2DNA molecule
TRANSLATION
41 Figure 10.10a
Amino acid
RNA
DNA strand
Polypeptide
Codon
TRANSCRIPTION
TRANSLATION
42
• Experiments have verified that the flow of
information from gene to protein is based on a
triplet code.
• A codon is a triplet of bases, which codes for one
amino acid.
From Nucleotides to Amino Acids: An Overview
© 2013 Pearson Education, Inc.
43 The Genetic Code
• The genetic code is the set of rules that convert a
nucleotide sequence in RNA to an amino acid
sequence.
• Of the 64 triplets,
– 61 code for amino acids and
– 3 are stop codons, instructing the ribosomes to end the polypeptide.
© 2013 Pearson Education, Inc.
44
Figure 10.11
Second base of RNA codonF
irst
base o
f R
NA
co
do
n
Phenylalanine(Phe)
Leucine(Leu)
Cysteine(Cys)
Leucine(Leu)
Isoleucine(Ile)
Valine(Val)
Met or start
Serine(Ser)
Proline(Pro)
Threonine(Thr)
Tyrosine(Tyr)
Histidine(His)
Glutamine(Gln)
Asparagine(Asn)
Alanine(Ala)
Stop Stop
Stop
Glutamicacid (Glu)
Asparticacid (Asp)
Lysine(Lys)
Arginine(Arg)
Tryptophan (Trp)
Arginine(Arg)
Serine(Ser)
Glycine(Gly)
Th
ird
base o
f R
NA
co
do
n
UUU
UUC
UUA
UUG
UAU
UAC
CAU
CAC
CAA
CAG
AAU
AAC
AAA
AAG
GAU
GAC
GAA
GAG
UGU
UGC
AGU
AGC
AGA
AGG
GGU
GGC
GGA
GGG
CGU
CGC
CGA
CGG
GCU
GCC
GCA
GCG
ACU
ACC
ACA
ACG
CCU
CCC
CCA
CCG
UCU
UCC
UCA
UCG
CUU
CUC
CUA
CUG
GUU
GUC
GUA
GUG
AUU
AUC
AUA
AUG
UAA
UAG
UGA
UGG
U C A G
U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
45
• Because diverse organisms share a common
genetic code, it is possible to program one species
to produce a protein from another species by
transplanting DNA.
The Genetic Code
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Figure 10.12 47 Transcription: From DNA to RNA
• Transcription
– makes RNA from a DNA template,
– uses a process that resembles the synthesis of a DNA strand during DNA replication, and
– substitutes uracil (U) for thymine (T).
© 2013 Pearson Education, Inc.
48
Transcription: From DNA to RNA
• RNA nucleotides are linked by the transcription
enzyme RNA polymerase.
© 2013 Pearson Education, Inc.
49
© 2013 Pearson Education, Inc.
Animation: Transcription
Right click slide / select “Play”
50
© 2013 Pearson Education, Inc.
Blast Animation: Transcription
Select “Play”
51 Figure 10.13
NewlymadeRNA
RNA nucleotides
RNA polymerase
Templatestrand of DNA
Direction oftranscription
(a) A close-up view of transcription (b) Transcription of a gene
RNApolymerase
Completed RNA
Growing RNATermination
Initiation TerminatorDNA
ElongationRNA
PromoterDNA
RNA polymerase
DNA of gene
2
1
3
52
Initiation of Transcription
• The “start transcribing” signal is a nucleotide
sequence called a promoter, which is
– located in the DNA at the beginning of the gene and
– a specific place where RNA polymerase attaches.
• The first phase of transcription is initiation, in which
– RNA polymerase attaches to the promoter and
– RNA synthesis begins.
© 2013 Pearson Education, Inc.
53RNA Elongation
• During the second phase of transcription, called
elongation,
– the RNA grows longer and
– the RNA strand peels away from its DNA template.
© 2013 Pearson Education, Inc.
54
Termination of Transcription
• During the third phase of transcription, called
termination,
– RNA polymerase reaches a special sequence of bases in the DNA template called a terminator,signaling the end of the gene,
– polymerase detaches from the RNA and the gene, and
– the DNA strands rejoin.
© 2013 Pearson Education, Inc.
55 The Processing of Eukaryotic RNA
• In the cells of prokaryotes, RNA transcribed from a
gene immediately functions as messenger RNA
(mRNA), the molecule that is translated into
protein.
• The eukaryotic cell
– localizes transcription in the nucleus and
– modifies, or processes, the RNA transcripts in the nucleus before they move to the cytoplasm for translation by ribosomes.
© 2013 Pearson Education, Inc.
56
• RNA processing includes
– adding a cap and tail consisting of extra nucleotides at the ends of the RNA transcript,
– removing introns (noncoding regions of the RNA), and
– RNA splicing, joining exons (the parts of the gene that are expressed) together to form messenger RNA (mRNA).
The Processing of Eukaryotic RNA
© 2013 Pearson Education, Inc.
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• RNA splicing is believed to play a significant role in
humans
– in allowing our approximately 21,000 genes to produce many thousands more polypeptides and
– by varying the exons that are included in the final mRNA.
The Processing of Eukaryotic RNA
© 2013 Pearson Education, Inc.
58
Figure 10.14
Transcription
Addition of cap and tail
Coding sequence
mRNA
DNA
Cytoplasm
Nucleus
Exons spliced together
Introns removed Tail
CapRNAtranscriptwith capand tail
59 Translation: The Players
• Translation is the conversion from the nucleic acid
language to the protein language.
© 2013 Pearson Education, Inc.
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Replication Transcription Translation
Template DNA DNA RNA
Polymer synthesized
DNA RNA Polypeptide
Monomernucleotide (deoxyribose)
nucleotide (ribose)
Amino acid
Polymerizing enzyme
DNA polymerase RNA polymerase ribosome
initiation site origin of replication promoter start site
termination site none terminator1 of 3 stop codons
61 62
63Messenger RNA (mRNA)
• Translation requires
– mRNA,
– ATP,
– enzymes,
– ribosomes, and
– transfer RNA (tRNA).
© 2013 Pearson Education, Inc.
64
Transfer RNA (tRNA)
• Transfer RNA (tRNA)
– acts as a molecular interpreter,
– carries amino acids, and
– matches amino acids with codons in mRNA using anticodons, a special triplet of bases that is complementary to a codon triplet on mRNA.
© 2013 Pearson Education, Inc.
65 Figure 10.15
tRNA polynucleotide(ribbon model)
Anticodon
Hydrogen bond
Amino acid attachment site
tRNA
(simplified
representation)
RNA polynucleotide chain
66
Ribosomes
• Ribosomes are organelles that
– coordinate the functions of mRNA and tRNA and
– are made of two subunits.
• Each subunit is made up of
– proteins and
– a considerable amount of another kind of RNA, ribosomal RNA (rRNA).
© 2013 Pearson Education, Inc.
67Ribosomes
• A fully assembled ribosome holds tRNA and
mRNA for use in translation.
© 2013 Pearson Education, Inc.
68
Figure 10.16a
tRNA binding sites
Ribosome
(a) A simplified diagram of a ribosome
Largesubunit
Smallsubunit
P site
mRNA binding
site
A site
69 Figure 10.16b
Next amino acidto be added to polypeptide
Growingpolypeptide
tRNA
mRNA
(b) The “players” of translation
Codons
70
Figure 10.16
Next amino acidto be added to polypeptide
Growing
polypeptide
tRNA
mRNA
tRNA
binding sites
Codons
Ribosome
(b) The “players” of translation
(a) A simplified diagram
of a ribosome
Large
subunit
Small
subunit
P site
mRNA
binding
site
A site
71 Translation: The Process
• Translation is divided into three phases:
1. initiation,
2. elongation, and
3. termination.
© 2013 Pearson Education, Inc.
72
Initiation
• Initiation brings together
– mRNA,
– the first amino acid with its attached tRNA, and
– two subunits of the ribosome.
• The mRNA molecule has a cap and tail that help
the mRNA bind to the ribosome.
© 2013 Pearson Education, Inc.
73 Figure 10.17
Start of geneticmessage
Tail
End
Cap 74
• Initiation occurs in two steps.
1. An mRNA molecule binds to a small ribosomal subunit, then a special initiator tRNA binds to the start codon, where translation is to begin on the mRNA.
2. A large ribosomal subunit binds to the small one, creating a functional ribosome.
Initiation
© 2013 Pearson Education, Inc.
75
© 2013 Pearson Education, Inc.
Animation: Translation
Right click slide / select “Play”
76
Figure 10.18
Initiator
tRNA
mRNA
Start codon
Met
P site
Small ribosomalsubunit
A site
Large ribosomalsubunit
21
77Elongation
• Elongation occurs in three steps.
– Step 1: Codon recognition. The anticodon of an incoming tRNA pairs with the mRNA codon at the A site of the ribosome.
© 2013 Pearson Education, Inc.
78
Figure 10.19
Amino acid
Anticodon
A site
Codons
mRNA
P site
Polypeptide
Codon recognition
Peptide bond formation
Translocation
Stop codon
New peptidebond
mRNAmovement
2
1
3
ELONGATION
79
– Step 2: Peptide bond formation.
– The polypeptide leaves the tRNA in the P site and
attaches to the amino acid on the tRNA in the A
site.
– The ribosome catalyzes the bond formation
between the two amino acids.
Elongation
© 2013 Pearson Education, Inc.
80
Figure 10.19a
mRNA
P site
Peptide bond formation
Polypeptide
ELONGATION
Codon recognition
A site
Codons
Anticodon
Amino acid
81
– Step 3: Translocation.
– The P site tRNA leaves the ribosome.
– The tRNA carrying the polypeptide moves from the
A to the P site.
Elongation
© 2013 Pearson Education, Inc.
82
Figure 10.19b
mRNAmovement
Translocation
ELONGATION
Stop codon
New peptidebond
83Termination
• Elongation continues until
– a stop codon reaches the ribosome’s A site,
– the completed polypeptide is freed, and
– the ribosome splits back into its subunits.
© 2013 Pearson Education, Inc.
84
Review: DNA→→→→ RNA→→→→ Protein
• In a cell, genetic information flows from
– DNA to RNA in the nucleus and
– RNA to protein in the cytoplasm.
© 2013 Pearson Education, Inc.
85 Figure 10.20-1
TranscriptionRNA polymerase
mRNA DNA
Intron
Nucleus1
86
Figure 10.20-2
TranscriptionRNA polymerase
mRNA DNA
Intron
Nucleus
mRNAIntron
TailCap
RNA processing2
1
87 Figure 10.20-3
TranscriptionRNA polymerase
mRNA DNA
Intron
Nucleus
mRNAIntron
TailCap
RNA processing
tRNA
Amino acid
Amino acid attachment
EnzymeATP
Anticodon
3
2
1
88
Figure 10.20-4
TranscriptionRNA polymerase
mRNA DNA
Intron
Nucleus
mRNAIntron
TailCap
RNA processing
tRNA
Amino acid
Amino acid attachment
EnzymeATP
Initiation of
translation
Ribosomalsubunits
Anticodon
A
3
4
2
1
89 Figure 10.20-5
TranscriptionRNA polymerase
mRNA DNA
Intron
Nucleus
mRNAIntron
TailCap
RNA processing
tRNA
Amino acid
Amino acid attachment
EnzymeATP
Initiation of
translation
Ribosomalsubunits
Anticodon
Codon
Elongation
Anticodon
A
3
4
5
2
1
90
Figure 10.20-6
TranscriptionRNA polymerase
mRNA DNA
Intron
Nucleus
mRNAIntron
TailCap
RNA processing
tRNA
Amino acid
Amino acid attachment
EnzymeATP
Initiation of
translation
Ribosomalsubunits
Termination
Anticodon
Codon
ElongationPolypeptide
Stopcodon
Anticodon
A
3
4 6
5
2
1
91
• As it is made, a polypeptide
– coils and folds and
– assumes a three-dimensional shape, its tertiary structure.
• Transcription and translation are how genes
control the structures and activities of cells.
Review: DNA→→→→ RNA→→→→ Protein
© 2013 Pearson Education, Inc.
92
Mutations
• A mutation is any change in the nucleotide
sequence of DNA.
• Mutations can change the amino acids in a protein.
• Mutations can involve
– large regions of a chromosome or
– just a single nucleotide pair, as occurs in sickle-cell disease.
© 2013 Pearson Education, Inc.
93 Figure 10.21
Normal hemoglobin DNA
mRNA
Normal hemoglobin
Mutant hemoglobin DNA
mRNA
Sickle-cell hemoglobin
Glu Val
94
• Mutations within a gene can be divided into two
general categories:
1. nucleotide substitutions (the replacement of one base by another) and
2. nucleotide deletions or insertions (the loss or addition of a nucleotide).
• Insertions and deletions can
– change the reading frame of the genetic message and
– lead to disastrous effects.
Types of Mutations
© 2013 Pearson Education, Inc.
95 Figure 10.22
mRNA and protein from a normal gene
Deleted
(a) Base substitution
Inserted
(b) Nucleotide deletion
(c) Nucleotide insertion
Met Lys Phe Gly Ala
Met Lys Phe Ser Ala
Met Lys Leu Ala
Met Lys Leu Trp Arg
96
Figure 10.22a
mRNA and protein from a normal gene
(a) Base substitution
Met Lys Phe Gly Ala
Met Lys Phe Ser Ala
97 Figure 10.22b
mRNA and protein from a normal gene
Deleted
(b) Nucleotide deletion
Met Lys Leu Ala
Met Lys Phe Gly Ala
98
Figure 10.22c
mRNA and protein from a normal gene
Met Lys Phe Gly Ala
(c) Nucleotide insertion
Met Lys Leu Trp Arg
Inserted
99Mutations
• (1) Wild-type gene
– The big red pig ate the red rag.
• (2) Base substitution
– The big res pig ate the red rag.
• (3) Base addition
– The big res dpi gat eth ere dra g.
• (4) Base deletion
– The big re-p iga tet her edr ag.
• 3 and 4 are know as frameshift mutations since
everything after the mutation is shifted and
would likely code for a new sequence of AAs© 2013 Pearson Education, Inc.
100
Mutagens
• Mutations may result from
– errors in DNA replication or recombination or
– physical or chemical agents called mutagens.
• Mutations
– are often harmful but
– are useful in nature and the laboratory as a source of genetic diversity, which makes evolution by natural selection possible.
© 2013 Pearson Education, Inc.
101 VIRUSES AND OTHER NONCELLULAR INFECTIOUS AGENTS
• Viruses share some, but not all, characteristics of
living organisms. Viruses
– possess genetic material in the form of nucleic acids wrapped in a protein coat,
– are not cellular, and
– cannot reproduce on their own.
© 2013 Pearson Education, Inc.
105
Figure 10.24a
Protein coat DNA
106 Animal Viruses
• Viruses that infect animals cells
– are a common cause of disease and
– may have RNA or DNA genomes.
• Many animal viruses have an outer envelope made
of phospholipid membrane, with projecting spikes
of protein.
© 2013 Pearson Education, Inc.
121
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