Download Handout #9 - Montana State University Billings

p53: Keeping Cancer in Check
The p53 protein:
•is a tumor suppressor
•associated with approximately 50 to 55 percent of human cancers.
•acts as a checkpoint in the cell cycle
July 8, 2002
Lung Cancer Patient Treated With Advexin Survives for 63
Months ... and Counting.
As part of a phase I trial conducted at The University of Texas M. D. Anderson
Cancer Center, the woman first received Advexin in 1997 in Houston after being
diagnosed with metastatic non-small cell lung cancer. Her tumor could not be
surgically removed because malignancy had spread within the lungs; the cancer
was uncontrolled after she was given multiple chemotherapy courses.
Advexin uses the p53 tumor suppressor gene to kill cancer cells or stops tumor
growth via an adenoviral delivery system that does not harm normal cells. Patients
are given large quantities of the nontoxic p53 gene, which then overtake cancer
cells and are cleared quickly from the body. In 20 clinical studies performed in
patients having eight different types of cancer, the drug was very well tolerated
and caused only minimal side effects
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
Microarray
Check gene exp.
Identify tumor and stage
Customize treatment
Mutation based therapy
Mutation based therapy
Wildtype
ATG, UUU, UUA
MET, PHE, LEU
nonsense
ATG, UUU, UAA
MET, PHE, STOP
missense
ATG, UUA, UUA
MET, LEU, LEU
frameshift
ATG, UCU, UUU, A
MET, SER, PHE
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.
DNA forensics
DNA fingerprinting
Person A
Person B
A
B
Figure 12.12B
DNA fingerprinting
Defendant’s
blood
Blood from
defendant’s clothes
Victim’s
blood
Figure 12.12B
DNA fingerprinting
Defendant’s
blood
Blood from
defendant’s clothes
Victim’s
blood
Figure 12.12B
DNA fingerprinting
Defendant’s
blood
Blood from
defendant’s clothes
Victim’s
blood
Figure 12.12B
DNA fingerprinting
Figure 12.12B
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
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
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
Canines
African wild dog Coyote
Wolf
Fox
Thousands to
millions of years
of natural selection
Ancestral canine
Hundreds to thousands
of years of breeding
(artificial selection)
Ancestral dog (wolf)
Jackal
Corn
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
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
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
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
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”
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
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
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
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
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
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
640 W
Ww
160
160 = 0.32
500
160 W + 160 w
ww
20
20 = 0.04
500
40 w
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
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
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
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
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