Evolution Of Human Health Evolutionary Analysis: Selection Thinking,

are thinking gaining recognition as useful

Timeline of Development in Health
tools in health research
Sciences

Timeline of Cholera Outbreak

Evolving Pathogens: Evasion of the Host’s

Flu Virus Evolution
Evolutionary Analysis: Phylogenetics, are
routinely used in health-related research.
- Evolutionary biology and modern
medicine were born at the same
time and have grown up in parallel.
The relevance of evolutionary
biology to human health Is deep.
Immune Response
- Influenza A is responsible for annual
flu epidemics and for occasional
global pandemics, such as
occurred in 1918, 1957, and 1968.
Most of us think of flu as merely an
annoyance—worse than a cold,
certainly, but not as bad as
chickenpox.
- The influenza A virus: The flu virus
has two major surface proteins,
hemagglutinin and neuraminidase.
The viral genome is carried on eight
separate pieces of RNA.
Hemagglutinin: Five antigenic sites,
regions recognized by the immune
system, appear in color.
Estimated Rate of Evolution and the
Phylogeny of the Frozen Flu Samples
(a) The molecular evolution of the influenza A
hemagglutinin gene as a function of time. The
surviving lineage accumulated nucleotide
substitutions at a constant rate. (b) A
phylogeny of flu viruses isolated between 1968
and 1987.
What allowed the surviving lineage to
endure while the other lineages
perished?
- According to the researchers’
hypothesis, it was nucleotide
substitutions resulting in amino acid
replacements in hemagglutinin’s
antigenic sites.
- Mutations continually generate
new lineages of flu, represented on
an evolutionary tree as new
branches. Among the lineages
alive at any given time, one (red
line) will ultimately survive; the rest
(gray lines) will eventually go
extinct.
- Which lineage will survive? Usually,
it is the one with the most amino
acid replacements in its
hemagglutinin antigenic sites
The Origin of Pandemic Flu Strains
- How is it possible that two flu strains
can have some genes that are
closely related and others that are
distantly related?
- The simplest explanation is that flu
strains can trade genes.
A phylogeny of flu virus nucleoprotein genes
Indicated for each viral strain is the host species,
the year of isolation, and the type of hemagglutinin
and neuraminidase it carries.
- Returning to the 1968 strains, note
that before the global pandemic
of that year, human flu viruses had
never carried H3.
- This suggests that it was the
acquisition of H3 from a nonhuman
 strain that allowed the 1968 flu to Evolutionary History of Each gene of the
infect people worldwide. 1918 Flu Virus
- What was the source of the H3
gene?

- The gene from the 1918 flu

branches near the base of the
clade that infects humans and
How do Human flu strains acquire genes pigs. This implies that all more
from bird strains? recent human and pig strains are
descended from the 1918 flu or one
- A popular hypothesis among flu of its close relatives.
researchers is that pandemics
begin when human strains and bird
strains simultaneously infect a pig,
swap genes with each other and
perhaps with pig strains, and later
move from pigs to people (Webster
et al. 1992).
- such a scenario was responsible for
- estimate the age of the common
generating a new human strain of
ancestor of the human and pig
H1N1 influenza A that appeared in
strains in the clade. This common
2009.
ancestor lived shortly before the
great pandemic.
Where did the virus that wrought havoc in
1918 and begat all subsequent human
influenzas come from?

Adaptedness of flu nucleoproteins to

humans vs birds (a) Phylogeny of the
nucleoprotein genes ana- lyzed. Colors
represent hosts as in (b). (b) The trade-off
in nucleoprotein adaptedness to humans
versus birds.
 Animal origins of human coronaviruses Evolving Pathogens: Antibiotic Resistance
- Antibiotics are chemicals that kill
bacteria by disrupting biochemical
processes.

Phylogenetic relationships in the

Coronavirinae subfamily Antibiotic Resistance: Biological Causes

Phylogenetic tree of the full-length Isoniazid Resistant Mycobacterium

genome sequences of SARS-CoV-2, tuberculosis
SARSr-CoVs and other betacoronaviruses.
 Plasmid Tn3 in Escherichia coli Evaluating the Costs of Resistance to
Bacteria

Evidence That Antibiotics Select for

Resistant Bacteria

- antibiotic resistance falls with

declining antibiotic use because
antibiotic resistance is costly to
bacteria. If resistance comes at a
cost, then when antibiotics are
absent, sensitive bacteria will have
Missense mutations of the rpoB gene higher fitness.
associated with resistance to Rifampicin
in M. tuberculosis Judicious Use of Antibiotics
- Bacteriologist Stuart Levy (1998)
recommends guidelines for the
limitation of antibiotic resistance.
- To avoid contracting foodborne
bacteria, consumers should wash
fruits and vegetables and avoid
raw eggs and undercooked meat.
- Consumers should use antibacterial
soaps and cleaners only when they
antibiotics select in favor of resistance, are needed to prevent infection in
then the level of resistance should track patients with compromised
antibiotic consumption immune systems.
- Patients should not request
antibiotics for viral infections, such
as colds or flu.
- When they take antibiotics,
patients should complete the
course of treatment. Patients
should not save antibiotics
prescribed for one infection and
use them to treat another.
- To avoid spreading infections from
patient to patient, doctors should
wash their hands thoroughly
between patients.
- Doctors should not prescribe - The shortsighted evolution
unneeded antibiotics, even when hypothesis.
patients ask.
- When they prescribe antibiotics,
doctors should use drugs that
target the narrowest possible range
of bacterial species.
- Doctors should isolate patients
infected with bacteria resistant to
several drugs to reduce the risk that
such bacteria will spread.
- The trade-off hypothesis.
Evolving Pathogens: Virulence
- Virulence is the harm done by a
pathogen to the host during the
course of an infection.
- Virulence varies dramatically
among human pathogens. Some
pathogens, like cholera and - A parasite that kills its host before
smallpox, are often lethal. Others, reproducing The Cordyceps fungus
including some herpes viruses and shown here invaded the body of a
cold viruses, produce few or no fly and grew inside. Finally, the
symptoms. fungus killed the fly and sprouted
- Evolutionary biologists investigating fruiting bodies that will release
virulence seek to explain this spores. Killing its host is not
diversity. necessarily detrimental to the
interests of a parasite.
Tissues as Evolving Populations of Cells
Adenosine deaminase (ADA)
- Adenosine deaminase (ADA),
encoded by a locus on chro-
mosome 20, is a housekeeping
enzyme normally made in all cells
of the body. ADA’s job is to recycle
purines
How Virulence Evolves
- The coincidental evolution
hypothesis
 adenosine deaminase deficiency

- A short piece of the gene

adenosine deaminase Point
mutations causing loss of function
appear in orange. Dad’s mutation
is in an intron/exon splice site.
Mom’s mutation results in an amino
acid substitution.
Possible Treatment for ADA deficiency
The evolutionary history of liver cancer
Metastasis
- The new tumor represents a new
population of cells. Because it was
founded by a single individual, this
new population will have low
genetic diversity. As it grows,
however, the population will
evolve.
- Like the population from which its
founder came, the new tumor will
accumulate genetic diversity as a
result of mutation and genetic drift.
- As in the original tumor population,
some of the new mutations may be
adaptive.
within an individual patient

Reconstructing the History of a Cancer

Inferred evolutionary history of tumor cell
lineages. Tan triangles represent rapidly
growing tumor cell populations.
nonsynonymous background mutations
include a frameshift in the gene for the
tumor suppressor p53 and amino acid
substitutions in genes encoding proteins
involved in immune defense and cell
anchoring.
Selection Thinking Applied to Humans
- researchers use selection thinking
to understand aspects of human
physiology and behavior relevant
to medicine and public health.
- Scientists using selection thinking,
also sometimes called the
adaptationist program, identify
traits that appear to be adaptive
- On the assumption that these traits
are products of natural selection,
the scientists test hypotheses about
how the traits enhance fitness.

Activity of mammalian cyclin-CDK

complexes through the course of the cell
cycle in cultured G0 cells induced to
divide by treatment with growth factors.

Adaptation to What Environment?

Adaptation to What Environment?

Overview of checkpoint controls in the
researchers’ estimate of the energy
cell cycle
sources in a typical hunter-gatherer diet,
compared with the energy sources in a
typical modern American diet.

While hunter-gatherers get more of their

energy from meat, they eat far leaner
meat, more fruits and vegetables, fewer
cereal grains, and fewer milk products.
 Adaptation to What Environment? why is the rate of breast cancer so high?
Here are two possible solutions to this
- Individuals carrying copies of allele
puzzle:
L68Q tend to die of strokes by their
early 30s. - Breast cancer may be caused by a
- This was not always the case, pathogen, such as a virus or
however. Two hundred years ago, bacterium.
adult carriers tended to live just as - Breast cancer may be a disease of
long, if not longer, than their civilization
spouses.
Adaptation and Medical Physiology:
Fever
An evolutionary perspective suggests two
interpretations of fever
- fever may reflect manipulation of
the host by the pathogen
- fever may be an
- Palsdottir and colleagues believe - adaptive defense
that a change in lifestyle is the likely
culprit. The researchers suspect
increased consumption of
carbohydrates and/or salt.
Breast Cancer

Research that ever is an adaptive

defense against disease

Fever and the Common Cold