Download Nucleic acids Nucleic acids are information

Nucleic acids
Nucleic acids are information-rich polymers
of nucleotides
DNA and RNA Serve as the blueprints for proteins and thus
control the life of a cell
DNA and RNA are polymers of nucleotides
– DNA is a nucleic acid
• Made of long chains of nucleotide monomers
Sugar-phosphate backbone
A
C
Phosphate group
Nitrogenous base
Sugar
DNA
nucleotide
A
C
Nitrogenous base
(A, G, C, or T)
Phosphate
group
O
H3C
O
T
T
G
G
O P O
O–
CH2
T
C
O
CH
HC
O
T
H
C
C
N
N
H
C
O
Thymine (T)
HC
CH
H
Sugar
(deoxyribose)
DNA nucleotide
DNA polynucleotide
1
DNA has four kinds of nitrogenous bases
• A, T, C, and G
H
O
H3C
H
C
C
C
H
H
N
N
C
C
C
C
H
O
N
N
H
H
N
N
H
C
O
N
H
H
Thymine (T)
C
C
C
N
C
N
H
O
N
N
C
H
N
H
H
C
C
N
N
C
H
Adenine (A)
Cytosine (C)
C
C
H
N
H
H
Guanine (G)
Purines
Pyrimidines
RNA is also a nucleic acid
• But has a slightly different sugar
• And has U instead of T
Nitrogenous base
(A, G, C, or U)
O
Phosphate
group
H
O
O
P
O
H
CH2
C
N
C
C
C
N
H
O
Key
Hydrogen atom
Carbon atom
Nitrogen atom
Oxygen atom
Phosphorus atom
Uracil (U)
O–
O
C H
H C
H C
C H
O
OH
Sugar
(ribose)
2
DNA is a double-stranded helix
– James Watson and Francis Crick
• Worked out the three-dimensional structure of DNA, based on
work by Rosalind Franklin
The structure of DNA
• Consists of two polynucleotide strands wrapped around each
other in a double helix
Twist
Figure 10.3C
3
The structure of DNA
• Consists of two polynucleotide strands wrapped around each
other in a double helix
• Hydrogen bonds between base hold the strands together
• Each base pairs with a complementary partner, A with T, and G
with C
G
C
T
Base
pair
T
C
G
C
C
G
A
T
A
A
T
–O
O O
–O P
O
H2C
A
T
A
T
O
O
– OP
O
H2C
Hydrogen bond
OH
A
T
O
O
O
– OP
O
H2C O
G
T
O OH
P
O
H2C O
A
A
G
C
O
C
O
G
A
T
G
CH2
O O–
OP
O
O CH2
O O–
O PO
O CH2
O O–
P
HO O
OH
C
T
A
O CH2
O O–
P
O
O
DNA replication depends on specific base pairing
G
C
T
A
A
T
C
G
C
C
G
A
T
T
OH
A
T
O O
–O P
O
H2C O
G
C
O
G
T
O OH
P
O
H2C O
–O
O
O
H2C O
O
– OP
A
G
C
O
A
A
– OP
T
A
O
O
H2C
T
O
OH
G
A
C
T
O CH2
O O–
P
O
O
A
T
CH2
O O–
OP
O
O CH2
O O–
O PO
O CH2
O –
PO
HO O
4
DNA replication depends on specific base pairing
DNA replication
– Starts with the separation of DNA strands
Then enzymes use each strand as a template
– To assemble new nucleotides into complementary strands
The Hershey-Chase experiment
Phage
Radioactive
protein
Bacterium
Empty
protein shell
Radioactivity
in liquid
Phage
DNA
DNA
Batch 1
Radioactive
protein
1 Mix radioactively
labeled phages with
bacteria. The phages
infect the bacterial
cells.
Batch 2
Radioactive
DNA
Centrifuge
2 Agitate in a blender to
separate phages outside
the bacteria from the cells
and their contents.
Pellet
3 Centrifuge the mixture
so bacteria form a pellet
at the bottom of the test
tube.
4 Measure the
radioactivity in
the pellet and
the liquid.
Radioactive
DNA
Centrifuge
Pellet
Radioactivity
in pellet
Figure 10.1B
5
– To replicate, the DNA helix must untwist
G
C
T
A
G
C
C
G
A
A
G
T
T
C
A
T
C
G
C
T
T A
A
TA
A
T
G
C
G
G
T
A
C
C
G
G
C G
C
A
T G
C
A
T
A
T
T
A A
T
6
– The DNA of the gene is transcribed into RNA
• Which is translated into the polypeptide
DNA
Transcription
RNA
Translation
Protein
Genetic information written in codons is translated into amino
acid sequences
– The “words” of the DNA “language”
• Are triplets of bases called codons
– The codons in a gene
• Specify the amino acid sequence of a polypeptide
Second base
UUU
UUC
U
C
Phe
Leu
CUU
First base
C
A
CUC
CUA
UCG
CCC
CCA
UAA Stop
CAU
Pro
CAC
CAA
CAG
AUU
ACU
AAU
AUC
Ile
AUA
ACC
ACA
Met or
start
AAC
Thr
AAA
ACC
AAG
GUU
GCU
GAU
GUC
GCC
GAC
GUA
Val
GCA
GCG
G
Tyr
UAG Stop
CCU
Leu
UAC
CCG
GUG
Figure 10.8A
Ser
CUG
AUG
G
UCC
UCA
UUA
A
UAU
UCU
Ala
His
Gln
Asn
Lys
Asp
Glu
Cys
U
C
UGA Stop
A
UGG Trp G
U
CGU
CGC
CGA
Arg
AGU
AGC
G
Ser
AGA
AGG
Arg
U
C
A
G
U
GGU
C
GGC
GGG
C
A
CGG
GGA
GAA
GAG
UGU
UGC
Third base
U
Gly
A
G
7
Transcription of a gene
Strand to be transcribed
T A
C
T
T C
A
A
A
A
T C
DNA
A
T
G A
A
G
T
T
T
T
A
G
A
G
Transcription
A
U
G A
A
G U
U
U
U
RNA
Start
condon
Stop
condon
Translation
Figure 10.8B
Polypeptide Met
Lys
Phe
Transcription of a gene
Exon Intron
Exon
Intron
Exon
DNA
Cap
RNA
transcript
with cap
and tail
Transcription
Addition of cap and tail
Introns removed
Tail
Exons spliced together
mRNA
Coding sequence
Nucleus
Cytoplasm
Figure 10.10
8
DNA molecule
Gene 1
Gene 2
Gene 3
DNA strand
A A A C C
G GC A A A A
Transcription
U U U
RNA
G GC C
GU U U U
Codon
Translation
Polypeptide
Amino acid
Figure 10.7
Mutations can change the meaning of genes
Mutations are changes in the DNA base sequence caused by
errors in DNA replication or recombination, or by mutagens
Normal hemoglobin DNA
C T
T
mRNA
C
A T
mRNA
G
Figure 10.16A
Mutant hemoglobin DNA
A
A
Normal hemoglobin
Glu
G
U
A
Sickle-cell hemoglobin
Val
9
10
11
Transcription regulates the expression of eukaryotic genes
during development to determine a cells FATE.
In female mammals, one X chromosome is inactive in each
cell
– An extreme example of DNA packing in interphase cells
Two cell populations
in adult
Early embryo
X chromosomes
Cell division
and random
X chromosome
inactivation
Active X
Inactive X
Inactive X
Allele for
orange fur
Active X
Orange
fur
Black fur
Allele for
black fur
12
These transcription factors regulate the expression of
eukaryotic genes during development to determine a cells
FATE.
Stem cells have great medical potential
– Like embryonic stem cells, adult stem cells can perpetuate
themselves in culture and give rise to differentiated cells
Blood cells
Adult stem
cells in bone
marrow
Nerve cells
Cultured
embryonic
stem cells
Heart muscle cells
Figure 11.12
Different culture
conditions
Different types of
differentiated cells
13
These transcription factors regulate the expression of
eukaryotic genes during development to determine a cells
FATE.
Cancer results from mutations in genes that control cell
division
– Cancer cells, which divide uncontrollably result from mutations in
genes whose protein products affect the cell cycle.
Proto-oncogene (a normal gene that promotes cell division)
Mutation within
the gene
New promoter
Oncogene
Hyperactive
growthstimulating
protein in
normal
amount
Gene moved to
new DNA locus,
under new controls
Multiple copies
of the gene
Normal growthstimulating
protein
in excess
Normal growthstimulating
protein
in excess
14
Tumor-Suppressor Genes
– Mutations that inactivate tumor suppressor genes have similar
effects as oncogenes
Tumor-suppressor gene
Mutated tumor-suppressor gene
Normal
growthinhibiting
protein
Defective,
nonfunctioning
protein
Cell division
under control
Cell division not
under control
Multiple genetic changes underlie the development of cancer
– Cancers result from a series of genetic changes in a cell lineage
– Accumulation of mutations can lead to cancer
– Colon cancer develops in a stepwise fashion
Chromosomes
Normal
cell
1
mutation
2
mutations
Figure 11.18B
3
mutations
4
mutations
Malignant
cell
15
Multiple genetic changes underlie the development of cancer
– Cancers result from a series of genetic changes in a cell lineage
– Accumulation of mutations can lead to cancer
– Colon cancer develops in a stepwise fashion
Colon wall
1
2
Cellular
changes:
Increased
cell division
Growth of polyp
Growth of malignant
tumor (carcinoma)
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second tumorsuppressor gene
inactivated
Figure 11.18A
3
Cancer in the United States
Table 11.20
16
The cell cycle control system
– A set of proteins within the cell that control the cell cycle
Control
Multiple genetic changes underlie the development of cancer
– Cancers result from a series of genetic changes in a cell lineage
– Accumulation of mutations can lead to cancer
– Colon cancer develops in a stepwise fashion
Colon wall
1
2
Cellular
changes:
Increased
cell division
Growth of polyp
Growth of malignant
tumor (carcinoma)
DNA
changes:
Oncogene
activated
Tumor-suppressor
gene inactivated
Second tumorsuppressor gene
inactivated
Figure 11.18A
3
17
Microarray
Check gene exp.
Identify tumor and stage
Customize treatment
The Human Genome Project:
– begun in 1990 and now largely completed,
– Genetic and physical mapping of chromosomes, followed by DNA
sequencing
– The data are providing insight into Development, evolution, and
many diseases
Table 12.17
18
About Cystic Fibrosis
•CF is among the most common life-threatening genetic disorders worldwide.
•CF affects 30,000 adults and children
•CF occurs in approximately one of every 3,500 live births, with approximately 1,000 new
cases diagnosed each year in the United States.
•Nonsense mutations cause CF in approximately 10% of patients.
•NO available therapy to correct defective CFTR production and function.
•Instead, available treatments for CF are designed to alleviate the symptoms of the
disease.
•chest physical therapy to clear the thick mucus from the lungs,
•antibiotics to treat lung infections
•a mucus-thinning drug designed to reduce the number of lung infections and
improve lung function.
19
DNA fingerprinting
Defendant’s
blood
Blood from
defendant’s clothes
Victim’s
blood
Figure 12.12B
20
DNA fingerprinting
•
•
•
•
•
RFLP analysis
• restriction fragment length polymorphism
• Oldest method, requires a lot of DNA
AmpFLP
• Amplified fragment length polymorphism
• Cheap
STR
• Short Tandem Repeats (1x 1018)
• Most common
Y-Chromosome
• Y chromosome analysis
• Paternal relationships among males
Mitochondrial DNA analysis
• Sequencing Mito DNA
• Maternal relationships, degraded samples
DNA fingerprinting
Figure 12.12B
21
Gene therapy
Evolution explains the unity and diversity of life
Charles Darwin
• Synthesized the theory of
evolution by natural selection
• He brought discussion of
evolution into the public
debate
22
A sea voyage helped Darwin frame his theory of evolution
– On his visit to the Galápagos Islands, Charles Darwin observed
many unique organisms
Figure 13.1A
Darwin’s main ideas can be traced back to the ancient
Greeks
– Aristotle and the Judeo-Christian culture believed that species are
fixed
– In the century prior to Darwin the study of fossils suggested that
life forms change
– Geologists proposed that a very old Earth is changed by gradual
processes
23
While on the voyage of the HMS Beagle in the 1830s Charles Darwin
observed similarities between living and fossil organisms and the
diversity of life on the Galápagos Islands
North
America
Great
Britain
Europe
Asia
ATLANTIC
OCEAN
PACIFIC
OCEAN
Africa
PACIFIC
OCEAN
Equator
Pinta
Marchena
Fernandina
0
0
PACIFIC
OCEAN
South
America
Genovesa
Equator
Santiago
Daphne
Islands
Pinzón
Isabela Santa
Santa
San
Cruz Fe
Cristobal
40 km
Florenza Española
40 miles
Australia
Andes
The
Galápagos
Islands
Cape of
Good Hope
Cape Horn
Tierra del Fuego
Tasmania
New
Zealand
Darwin proposed natural selection as the mechanism of
evolution
– Darwin observed that organisms
•
Produce more offspring than the environment can support
•
Vary in many characteristics that can be inherited
– Darwin reasoned that natural selection
•
Results in favored traits being represented more and more and
unfavored ones less and less in ensuing generations of
organisms
– Darwin found convincing evidence for his ideas in the results of
artificial selection
•
The selective breeding of domesticated plants and animals
24
Canines
African wild dog Coyote
Wolf
Fox
Jackal
Thousands to
millions of years
of natural selection
Ancestral canine
Hundreds to thousands
of years of breeding
(artificial selection)
Ancestral dog (wolf)
Corn
25
Darwin proposed that living species are
descended from earlier life forms and
that natural selection is the
mechanism of evolution
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Skull of Homo erectus
26
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Ammonite casts
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Dinosaur tracks
27
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Dinosaur tracks
http://paleo.cc/paluxy/ovrdino.htm
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Dinosaur tracks
http://paleo.cc/paluxy/ovrdino.htm
28
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Dinosaur tracks
http://paleo.cc/paluxy/ovrdino.htm
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Fossilized organic matter of a leaf
29
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
Insect in amber
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
“Ice Man”
30
The study of fossils provides strong evidence for evolution
– Fossils and the fossil record strongly support the theory of evolution
A Skull of Homo
erectus
B Petrified tree
E Fossilized organic
matter of a leaf
C Ammonite casts
D Dinosaur tracks
F Insect in amber
G “Ice Man”
The fossil record
•
Reveals that organisms have evolved in a historical sequence
Figure 13.3H
31
A mass of other evidence reinforces the evolutionary view of life
Biogeography
– Biogeography, the geographic distribution of species
•
Suggested to Darwin that organisms evolve from common
ancestors
– Darwin noted that Galápagos animals
•
Resembled species of the South American mainland
more than animals on similar but distant islands
A mass of other evidence reinforces the evolutionary view of life
Biogeography
– Biogeography, the geographic distribution of species
•
Suggested to Darwin that organisms evolve from common
ancestors
– Darwin noted that Galápagos animals
•
Resembled species of the South American mainland
more than animals on similar but distant islands
Comparative anatomy
– Comparative anatomy
•
Is the comparison of body structures in different species
– Homology
•
Is the similarity in characteristics that result from common
ancestry
32
Homologous structures
•
Figure 13.4A
Are features that often have different functions but are
structurally similar because of common ancestry
Human
Cat
Whale
Bat
Comparative embryology
•
•
Is the comparison of early stages of development among
different organisms Many vertebrates
Have common embryonic structures
Pharyngeal
pouches
Post-anal
tail
Human embryo
Chick embryo
Figure 13.4B
33
Molecular Biology
– Comparisons of DNA and amino acid sequences between different
organisms
•
Reveal evolutionary relationships
Table 13.4
Scientists can observe natural selection in action
– Camouflage adaptations that evolved in different environments
•
Are examples of the results of natural selection
Figure 13.11
34
Populations are the units of evolution
– A population
•
Is a group of individuals of the same species living in the
same place at the same time
– A species is a group of populations
•
Whose individuals can interbreed and produce fertile
offspring
– Population genetics
•
Studies how populations change genetically over time
•
A gene pool is the total collection of genes in a population
at any one time
The gene pool of a nonevolving population remains constant
over the generations
In a nonevolving population
The shuffling of alleles that accompanies sexual reproduction
does not alter the genetic makeup of the population
Figure 13.7A
Webbing
No webbing
35
Hardy-Weinberg equilibrium
– States that the shuffling of genes during sexual reproduction does not
alter the proportions of different alleles in a gene pool
Figure 13.7A
Webbing
No webbing
Phenotypes
Genotypes
WW
Number of animals 320
(total = 500)
320 = 0.64
Genotype frequencies
500
Number of alleles
in gene pool
(total = 1,000)
Allele frequencies
Figure 13.7B
640 W
Ww
ww
160
20
160 = 0.32
500
160 W + 160 w
800 = 0.8 W
1,000
20 = 0.04
500
40 w
200 = 0.2 w
1,000
The Hardy-Weinberg equation is useful in public health
science
– Public health scientists use the Hardy-Weinberg equation
•
To estimate frequencies of disease-causing alleles in the
human population
36
The Hardy-Weinberg equation is useful in public health
science
– Public health scientists use the Hardy-Weinberg equation
•
To estimate frequencies of disease-causing alleles in the
human population
37
In addition to natural selection, both genetic drift and gene
flow can contribute to evolution
– Genetic drift
•
Is a change in the gene pool of a population due to chance
•
Can alter allele frequencies in a population
•
Can cause the bottleneck effect or the founder effect
Original
population
Bottlenecking
event
Surviving
population
In addition to natural selection, genetic drift and gene flow
can contribute to evolution
– Genetic drift
•
Is a change in the gene pool of a population due to chance
•
Can alter allele frequencies in a population
•
Can cause the bottleneck effect or the founder effect
– Gene flow
•
Is the movement of individuals or gametes between populations
•
Can alter allele frequencies in a population
38
In addition to natural selection, genetic drift and gene flow
can contribute to evolution
– Genetic drift
•
Is a change in the gene pool of a population due to chance
•
Can alter allele frequencies in a population
•
Can cause the bottleneck effect or the founder effect
– Gene flow
•
Is the movement of individuals or gametes between populations
•
Can alter allele frequencies in a population
– Natural selection
•
Leads to differential reproductive success in a population
•
Can alter allele frequencies in a population
Endangered species often have low genetic variability
– May reduce the capacity of endangered species to survive as
humans continue to alter the environment
39
Genetic variation is extensive in most populations
– Many populations exhibit polymorphism
•
Different forms of phenotypic characteristics
Figure 13.11
The evolution of antibiotic resistance in bacteria is a serious
public health concern
– The excessive use of antibiotics
•
Is leading to the evolution of antibiotic-resistant bacteria
40