Resistance of Mycobacterium tuberculosis to antibiotics n This bacterium that causes tuberculosis...
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Resistance of Mycobacterium tuberculosis to antibiotics
This bacterium that causes tuberculosis has been one of the scourges of humankind
• Caused 25% of all deaths in New York City in 1804
• Caused 33% of the deaths in Paris in the 19th century
It still kills more people than any other viral or bacterial disease
However, improved nutrition and sanitation caused a decline in TB in industrialized countries
The drugs rifampin and isoniazid are effective against the TB bacteria
Incidence of TB infections in 1997 (per 100,000 people)
Less than 1010-24
25-49
50-99100-250More than 250
Figure 21.6
In the late 1980’s, the World Health Organization declared TB a global health emergency
A number of strains of M. tuberculosis were largely or completely resistant to rifampin and isoniazid
The case of an HIV-positive man in Baltimore provides insight into the acquisition of resistance by M. tuberculosis
This man was diagnosed with an acute case of TB
A 39-month regimen of antibiotics resulted in clear x-rays of his lungs and no sign of the bacteria in his body - the antibiotics seemed to have cleared the infection
Two months later, the man was readmitted to the hospital with tuberculosis-like symptoms
Despite aggressive antibiotic treatment, the man died 10 days later
The man’s physician and his research team analyzed the DNA from the resistant M. tuberculosis from the man as well as DNA from M. tuberculosis cells taken from the man when he was first admitted
The research team sequenced much of the DNA from the two strains and found only a single difference, a point mutation at a locus that codes for a portion of RNA polymerase (the protein that transcribes DNA to mRNA)
The mutation changed a TCG codon to TTG
The mutant RNA polymerase had leucine instead of serine at the 153rd amino acid in the polypeptide chain
Rifampin acts by binding to the RNA polymerase of M. tuberculosis
The substitution of leucine for a serine apparently kept the rifampin from binding tightly to the RNA polymerase
The chain of events
The mutation arose early in the course of the infection
The mutant cells stayed at low frequency during the initial infection
After antibiotic treatment began, the mutant cells had a selective advantage
The mutant cells grew in population size, eventually causing a relapse of TB for the patient
Being resistant to rifampin, antibiotic treatment was ineffective
Did evolution by natural selection occur? Was there variation in the population?
• Yes, there were resistant and non-resistant strains
Was this variation heritable?
• Yes, the researchers showed that the phenotypes of the two strains were due to variation in their genotypes
Did natural selection occur?
• Yes, only a small fraction of the M. tuberculosis cells survived the first round of antibiotics
When selection occurred, did a non-random subset of the population survive better and reproduce more?
• It is clear that cells with the mutant allele conferring antibiotic resistance increased through time
In tundra habitats above timberline, the alpine skypilot is pollinated primarily by bumblebees.
In forested habitats below timberline, the alpine skypilot is pollinated primarily by flies.
Below-timberline flower: small and skunky-smelling Flower size (mm)
Nu
mb
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10 12 14 16 18 20 22
10
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Tundra flower: big and sweet-smelling
Flower size (mm)
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24201612 8 4 0
10 12 14 16 18 20 22
Figure 21.7 a,b
Tundra flower: big and sweet-smelling
In tundra habitats above timberline, the alpine skypilot ispollinated primarily by bumblebees.
Tundra pollinator: bumblebeeFlower size (mm)
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2824201612 8 4 0
10 12 14 16 18 20 22
Figure 21.7a
In forested habitats below timberline, the alpine skypilot ispollinated primarily by flies.
Below-timberline flower:small and skunky-smelling
Below-timberline pollinator: flyFlower size (mm)
Nu
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10 12 14 16 18 20 22
10
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Figure 21.7b
Large flowersSmall flowers
Short stems Tall stems
–3 –2 –1 0 1 2–4
Size score
110
100
80
60
40
20
0
Bee
vis
its
rece
ived
Figure 21.8
0 20 40 60 80 100 110
Bee visits received
1.0
0.8
0.6
0.4
0.2
0
Rel
ativ
e fi
tnes
s (f
ecu
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Figure 21.9
8 10
8
10
Mother’s flower size (mm)
Off
spri
ng
’s f
low
er s
ize
(mm
)
12 14 16 18
12
14
16
18
Figure 21.10
9 11 13 15 17
9 11 13 15 17
0
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Flower size (mm)
Flower size (mm)
4. Measure flower sizes and plot data.Average = 13.1 mm
4. Measure flower sizes and plot data.Average = 14.4 mm
3. Plant seedlingsinto randomly assigned locations in the field.
3. Plant seedlingsinto randomly assigned locations in the field.
2. Collect seeds;germinate ingreenhouse
2. Collect seeds;germinate ingreenhouse
POLLINATION EXPERIMENT: CONTROL GROUP
POLLINATION EXPERIMENT: EXPERIMENTAL GROUP
1. Hand pollinate a large, randomsample of skypilots.
1. Allow bees to pollinate a largesample of skypilots.
Figure 21.11