Lecture 19
Evolution and human health
The evolution of flu viruses
The evolution of flu viruses
Google Flu Trends data
US data
Check out:
http://www.google.org/flutrends/
The evolution of flu viruses
• the evolution of viruses and their hosts is a form of
antagonistic coevolution.
The evolution of flu viruses
• the evolution of viruses and their hosts is a form of
antagonistic coevolution.
• host-pathogen coevolution is also referred to as an
“evolutionary arms race”.
The evolution of flu viruses
• the evolution of viruses and their hosts is a form of
antagonistic coevolution.
• host-pathogen coevolution is also referred to as an
“evolutionary arms race”.
Adaptation
Host


Counter Adaptation
Pathogen
The evolution of flu viruses
• the evolution of viruses and their hosts is a form of
antagonistic coevolution.
• host-pathogen coevolution is also referred to as an
“evolutionary arms race”.
Example: the influenza A virus
The evolution of flu viruses
• the evolution of viruses and their hosts is a form of
antagonistic coevolution.
• host-pathogen coevolution is also referred to as an
“evolutionary arms race”.
Example: the influenza A virus
• influenza A is a retrovirus with 11 genes (on 8 RNA
strands).
The evolution of flu viruses
• the evolution of viruses and their hosts is a form of
antagonistic coevolution.
• host-pathogen coevolution is also referred to as an
“evolutionary arms race”.
Example: the influenza A virus
• influenza A is a retrovirus with 11 genes (on 8 RNA
strands).
• responsible for annual flu epidemics (killing about 30,000 to
35,000 Americans per year).
Influenza A virus also causes serious
global pandemics:
Influenza A virus also causes serious
global pandemics:
Year
Spanish flu
1918
Deaths in US
500,000
Influenza A virus also causes serious
global pandemics:
Year
Deaths in US
Spanish flu
1918
500,000
Asian flu
1957
60,000
Influenza A virus also causes serious
global pandemics:
Year
Deaths in US
Spanish flu
1918
500,000
Asian flu
1957
60,000
Hong Kong flu
1968
80,000
The influenza A virus
N
H
The influenza A virus
N
H
The evolution of antigenic sites
The evolution of antigenic sites
• influenza A’s major coat protein is hemagglutinin.
The evolution of antigenic sites
• influenza A’s major coat protein is hemagglutinin.
• hemagglutinin is the main target of our immune system.
The evolution of antigenic sites
• influenza A’s major coat protein is hemagglutinin.
• hemagglutinin is the main target of our immune system.
• amino acid sites in hemagglutinin that our immune system
recognizes (and remembers) are called antigenic sites.
Locations of antigenic
sites in hemagglutinin
molecule
Phylogenetic analysis of influenza A
Phylogenetic analysis of influenza A
• Fitch et al. (1991) examined the phylogenetic relationships
among flu strains over a 20-year period using hemagglutinin
sequences.
Phylogenetic analysis of influenza A
• Fitch et al. (1991) examined the phylogenetic relationships
among flu strains over a 20-year period using hemagglutinin
sequences.
• this is equivalent to 20 million years of human
evolution!
Hemagglutinin evolved at a constant rate!
Hemagglutinin evolved at a constant rate!
Is this neutral
evolution?
Hemagglutinin evolved at a constant rate!
Is this neutral
evolution?
NOT LIKELY!
Annual flu epidemics arise from a single lineage!
Why did only a single flu strain persist?
Why did only a single flu strain persist?
• due to differences in mutations at antigenic vs. nonantigenic sites?
Why did only a single flu strain persist?
• due to differences in mutations at antigenic vs. nonantigenic sites?
Surviving
lineage
Extinct
lineages
Why did only a single flu strain persist?
• due to differences in mutations at antigenic vs. nonantigenic sites?
Surviving
lineage
antigenic sites
33
Extinct
lineages
31
Why did only a single flu strain persist?
• due to differences in mutations at antigenic vs. nonantigenic sites?
Surviving
lineage
antigenic sites
non-antigenic sites
33
10
Extinct
lineages
31
35
Why did only a single flu strain persist?
• due to differences in mutations at antigenic vs. nonantigenic sites?
Surviving
lineage
antigenic sites
non-antigenic sites
33
10
43
Extinct
lineages
31
35
66
Why did only a single flu strain persist?
• due to differences in mutations at antigenic vs. nonantigenic sites?
Surviving
lineage
antigenic sites
non-antigenic sites
33
10
43
Extinct
lineages
31
35
66
Conclusion: The surviving lineage had significantly
more mutations at antigenic sites
Positive selection in the hemagglutinin
gene
Positive selection in the hemagglutinin
gene
• positive selection occurs when the rate of replacement
substitution exceeds the rate of silent substitution.
Positive selection in the hemagglutinin
gene
• positive selection occurs when the rate of replacement
substitution exceeds the rate of silent substitution.
• in influenza A, there are 18 codons exhibiting higher rates
of replacement substitution!
Positive selection in the hemagglutinin
gene
• positive selection occurs when the rate of replacement
substitution exceeds the rate of silent substitution.
• in influenza A, there are 18 codons exhibiting higher rates
of replacement substitution!
• why is this important?
Positive selection in the hemagglutinin
gene
• positive selection occurs when the rate of replacement
substitution exceeds the rate of silent substitution.
• in influenza A, there are 18 codons exhibiting higher rates
of replacement substitution!
• why is this important?
• because this allows us to predict surviving strains and thus
make flu vaccines!
Strains that persist have the most changes
in hemagglutinin antigenic sites
A phylogeny of
influenza A based on
the nucleoprotein
gene
*
*
*
*
*
*
*
*
**
*
*
Influenza A can move between humans, birds, and
pigs

Where did H3
come from?
H3 jumped into humans from birds
Influenza A can move between humans, birds
and pigs
The origin of pandemic flu strains
Human strain


Bird strain
Recombination in swine host

Reinfect human host
H1N1 is a triple-reassortment virus
H1N1 is a triple-reassortment virus
Segment
Origin
PB2
PB1
PA
HA
NP
NA
MP
NS
Avian North America
Human circa 1993
Swine Eurasia
Swine North America
Swine Eurasia
Swine Eurasia
Swine Eurasia
Swine Eurasia
The evolution of virulence
The evolution of virulence
• virulence is a term that describes the effect a
pathogen has on its host.
The evolution of virulence
• virulence is a term that describes the effect a
pathogen has on its host.
high virulence → major effect on host’s fitness
The evolution of virulence
• virulence is a term that describes the effect a
pathogen has on its host.
high virulence → major effect on host’s fitness
low virulence → minor effect on its host’s fitness
The evolution of virulence
• virulence is a term that describes the effect a
pathogen has on its host.
high virulence → major effect on host’s fitness
low virulence → minor effect on its host’s fitness
Example: rabbits and the myxoma virus in Australia
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
• in 1859, 12 rabbits were bought by Mr. Thomas Austin.
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
• in 1859, 12 rabbits were bought by Mr. Thomas Austin.
• 6 years later, there were 30,000!
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
• in 1859, 12 rabbits were bought by Mr. Thomas Austin.
• 6 years later, there were 30,000!
• they escaped from his farm and exploded in abundance all
over the country.
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
• in 1859, 12 rabbits were bought by Mr. Thomas Austin.
• 6 years later, there were 30,000!
• they escaped from his farm and exploded in abundance all
over the country.
• the myxoma virus was introduced in the 1950’s to control
the rabbit population.
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
Virulence grade
high
I
low
II
IIIa
IIIb
IV
V
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
Virulence grade
high
1950
low
I
II
IIIa
IIIb
IV
V
100
0
0
0
0
0
The evolution of virulence
Example: rabbits and the myxoma virus in Australia
Virulence grade
high
low
I
II
IIIa
IIIb
IV
V
1950
100
0
0
0
0
0
1964
0
34.0
31.3
8.3
0.3 26.0
The evolution of virulence
• virulence is a term that describes the effect a
pathogen has on its host.
high virulence → major effect on host’s fitness
low virulence → minor effect on its host’s fitness
• three models have been proposed to account for the
evolution of virulence.
1. The coincidental evolution hypothesis
1. The coincidental evolution hypothesis
• the virulence of many human pathogens is a result of
selection acting on that pathogen in a different
environment.
1. The coincidental evolution hypothesis
• the virulence of many human pathogens is a result of
selection acting on that pathogen in a different
environment.
Example: tetanus
1. The coincidental evolution hypothesis
• the virulence of many human pathogens is a result of
selection acting on that pathogen in a different
environment.
Example: tetanus
• caused by a soil bacteria Clostridium tetani.
1. The coincidental evolution hypothesis
• the virulence of many human pathogens is a result of
selection acting on that pathogen in a different
environment.
Example: tetanus
• caused by a soil bacteria Clostridium tetani.
• produces a deadly toxin not directed at humans but at
something in the soil.
2. The short-sighted evolution hypothesis
2. The short-sighted evolution hypothesis
• since pathogens reproduce within hosts, traits that increase
their short-term fitness may actually be detrimental.
2. The short-sighted evolution hypothesis
• since pathogens reproduce within hosts, traits that increase
their short-term fitness may actually be detrimental.
• the virus is “short-sighted” and virulence higher than
expected.
2. The short-sighted evolution hypothesis
• since pathogens reproduce within hosts, traits that increase
their short-term fitness may actually be detrimental.
• the virus is “short-sighted” and virulence higher than
expected.
Example: poliovirus.
2. The short-sighted evolution hypothesis
• since pathogens reproduce within hosts, traits that increase
their short-term fitness may actually be detrimental.
• the virus is “short-sighted” and virulence higher than
expected.
Example: poliovirus.
• normally infects cells that line the digestive tract and cause
few symptoms.
2. The short-sighted evolution hypothesis
• since pathogens reproduce within hosts, traits that increase
their short-term fitness may actually be detrimental.
• the virus is “short-sighted” and virulence higher than
expected.
Example: poliovirus.
• normally infects cells that line the digestive tract and cause
few symptoms.
• occasionally, the virus infects cells of the nervous system
with tragic consequences.
3. The trade-off hypothesis
3. The trade-off hypothesis
• pathogens should evolve to the point where fitness costs to
the host are balanced by its capacity to propagate itself to
other hosts.
3. The trade-off hypothesis
• pathogens should evolve to the point where fitness costs to
the host are balanced by its capacity to propagate itself to
other hosts.
• pathogens may thus evolve to where they harm their hosts
considerably.
3. The trade-off hypothesis
• pathogens should evolve to the point where fitness costs to
the host are balanced by its capacity to propagate itself to
other hosts.
• pathogens may thus evolve to where they harm their hosts
considerably.
An experiment: E. coli and the phage f1 by Messenger et al.
(1999).
3. The trade-off hypothesis
• pathogens should evolve to the point where fitness costs to
the host are balanced by its capacity to propagate itself to
other hosts.
• pathogens may thus evolve to where they harm their hosts
considerably.
An experiment: E. coli and the phage f1 by Messenger et al.
(1999).
• phage f1 can propagate both vertically (parent to daughter
cell) and horizontally (to a new host).
Treatment 1: 8 day vertical () + brief horizontal ()









Treatment 1: 8 day vertical () + brief horizontal ()









Treatment 2: 1 day vertical () + brief horizontal ()


Treatment 1: 8 day vertical () + brief horizontal ()









Treatment 2: 1 day vertical () + brief horizontal ()


After 24 days measured:
Treatment 1: 8 day vertical () + brief horizontal ()









Treatment 2: 1 day vertical () + brief horizontal ()


After 24 days measured:
1. Phage virulence (growth rate of infected hosts).
Treatment 1: 8 day vertical () + brief horizontal ()









Treatment 2: 1 day vertical () + brief horizontal ()


After 24 days measured:
1. Phage virulence (growth rate of infected hosts).
2. Phage growth rate (rate of virion secretion from infected
hosts).
Trade-off between virulence and
reproductive rate in phage f1
What factors can select for increased
virulence?
What factors can select for increased
virulence?
1. Live host not needed for transmission
What factors can select for increased
virulence?
1. Live host not needed for transmission
Examples: ebola virus, parasitic fungi
What factors can select for increased
virulence?
1. Live host not needed for transmission
Example: ebola virus, parasitic fungi
2. Multiple infections in same host
What factors can select for increased
virulence?
1. Live host not needed for transmission
Example: ebola virus, parasitic fungi
2. Multiple infections in same host
• leads to competition among pathogens within hosts
What factors can select for increased
virulence?
1. Live host not needed for transmission
Example: ebola virus, parasitic fungi
2. Multiple infections in same host
• leads to competition among pathogens within hosts
3. Transmission is “horizontal” (i.e., from
individual to individual), not “vertical” (i.e.,
parent to offspring)