
Chapter 1 of Zimmer and Emlen text--The
virus and the whale: how scientists study
evolution.

Any change in the inherited traits
(genetic structure) of a population that
occurs from one generation to the next.

Note that evolution is a population
process that occurs from generation to
generation.

The above definition is a definition of
Microevolution.
The microevolutionary changes in
genetic structure of a population over
time can lead to substantial changes in
the morphology of organisms over time
and the origin of new species.
 Such changes are referred to as
Macroevolution.

Evolution explains the diversity of life. All
living things are related to each other
and are the products of millions of years
of evolution.
 Understanding evolution allows us to
understand why the living world is the
way it is. We can understand e.g., the
similarities and differences between
species, as well as their adaptations and
their distributions.


There are also practical reasons to study
evolution.

Evolution allows us to understand the
evolution of disease organisms such as
viruses and bacteria and combat them.
Evolution also gives us insight into such
“big” questions as:
 “How did we get here?” and
 “How did thought and language
evolve?”


Your text has a nice discussion of the
evolution of the flu virus. You need to
read it and be familiar with it.

We will discuss a different example in
class– the HIV virus to illustrate the
process of natural selection.
Acquired immune deficiency syndrome
(AIDS) caused by Human
Immunodeficiency Virus (HIV).
 Disease first described in 1981.
 Transmitted through transfer of bodily
fluids.
 Immune system attacked. Victim dies of
secondary infections.

More than 60 million people so far
infected.
 Mortality so far about 20 million.
 Projected mortality by 2020 --90 million
lives
 Responsible for about 5% of all deaths
worldwide.
 Approx. 8,000 deaths per day.

HIV, like all viruses, is an intracellular
parasite
 Parasitizes macrophages and T-cells of
immune system
 Uses cells enzymatic machinery to copy
itself. Kills host cell in process.

HIV binds to two protein receptors on
cell’s surface : CD4 and a coreceptor,
usually CCR5.
 Host cell membrane and viral coat fuse
and virus contents enter cell.

RNA genome
 Reverse transcriptase: transcribes viral
RNA into DNA
 Integrase: this enzyme splices DNA into
host DNA
 Protease: this enzyme involved in
production of viral proteins

Viral DNA inserted in host DNA produces
HIV mRNA and all components of virus
 Viral particles self assemble and bud
from host cell.

HIV budding from
human immune cell
Because HIV hijacks the host’s own
enzymatic machinery: ribosomes,
transfer RNAs, polymerases, etc. it is hard
to treat.
 Drugs that targeted these would target
every cell in the hosts body


Three stages
› Acute
› Chronic
› AIDS
Viral load increases rapidly
 CD4 helper T cell level declines
 Immune system mobilizes
 Viral load declines, CD4 T cell level
increases

HIV not eliminated
 Viral load increases slowly
 CD4 helper T cell levels slowly decline

CD4 helper T cell level drops so low
immune system fails.
 Patient vulnerable to all infections
 Life expectancy of only 2-3 years

Human body responds to infection with
HIV by mobilizing the immune system.
 The immune system destroys virus
particles floating in bloodstream and
also destroys cells infected with virus.
 Unfortunately, the cells that HIV infects
are critical to immune system function.

HIV invades immune system cells
especially helper T cells.
 These helper T cells have a vital role in
the immune system.
 When a helper T cell is activated (by
having an antigen [a piece of foreign
protein] presented to it, it begins to
divide into memory T cells and effector T
cells.

Memory T cells do not engage in current
fight against the virus.
 Instead they are long-lived and can
generate an immune response quickly if
the same foreign protein is encountered
again.


Effector T cells engage in attacking the
virus. They produce signaling molecules
called chemokines that stimulate B cells to
produce antibodies to the virus.

Effector T cells also stimulate macrophages
to ingest cells infected with the virus.

In addition effector T cells stimulate killer T
cells to destroy infected cells displaying viral
proteins.
First round of infection with HIV reduces
the pool of CD4 Helper T cells (those that
can recognize and attack HIV).
 Loss of CD4 cells costly, but immune
system now primed to recognize viral
protein.
 What’s the problem? Why isn’t HIV
eliminated?

Virus mutates and the proteins on its
outer surface (gp120 and gp41) change.
 These surface proteins are not
recognized by the immune systems’
memory cells.
 Mutants survive immune system
onslaught and begin new round of
infection


Each round of infection reduces the
numbers of helper T cells because they are
infected by virus and destroyed.

Furthermore, because each lineage of T
cells has a limited capacity for replication
after a finite number of rounds of
replication the body’s supply of helper T
cells becomes exhausted and the immune
system eventually is overwhelmed and
collapses.
AZT (azidothymidine) was the first HIV
wonder drug
 It works by interfering with HIV’s reverse
transcriptase, which is the enzyme the
virus uses to convert its RNA into DNA so it
can be inserted in the host’s geneome.

AZT is similar to thymidine (one of 4 bases
of DNA nucleotides) but it has an azide
group (N3) in place of hydroxyl group
(OH).
 An AZT molecule added to DNA strand
prevents the strand from growing. The
azide blocks the attachment of next
nucleotide in the DNA chain.
 If DNA cannot be completed, viral
proteins cannot be made.

AZT successful in tests although with
serious side effects.
 But patients quickly stopped responding
to treatment.
 Evolution of AZT-resistant HIV in patients
usually took only about 6 months.

The reverse transcriptase gene in
resistant strains differs genetically from
non-resistant strains.
 Mutations are located in active site of
reverse transcriptase.
 These changes selectively block the
binding of AZT to DNA but allow other
nucleotides to be added.

HIV reverse transcriptase very error
prone.
 About half of all DNA transcripts
produced contain an error (mutation).
 HIV has the highest mutation rate known
for any biological entity.
 There is thus enormous VARIATION in the
HIV population in a patient.

High mutation rate makes the
occurrence just by chance of AZTresistant mutations almost certain.
 NATURAL SELECTION now starts to act in
the presence of AZT

The presence of AZT suppresses
replication of non-resistant strains.
 Resistant strains are BETTER ADAPTED to
the environment.
 Resistant strains reproduce more rapidly.
There is thus DIFFERENTIAL REPRODUCTIVE
SUCCESS of HIV strains. Resistant strains
produce more offspring.


Resistant strains replicate and pass on
their resistant genes to the next
generation.

Thus resistance is HERITABLE.

AZT-resistant strains replace non-resistant
strains. The HIV gene pool changes from
one generation to the next.

EVOLUTION has occurred: Remember
evolution is change in the gene pool
from one generation to the next.
Evolution of HIV population in an individual patient
There is variation in population – some
members of population better adapted
than others
 That variation affects reproductive success
– there is differential reproductive success
as a result of natural selection.
 Because the variation is heritable –
beneficial alleles passed to offspring and
alleles become more common in next
generation.


Several different types of drugs have
been developed to treat HIV.
› Reverse transcriptase inhibitors (e.g. AZT).
› Protease inhibitors (prevent HIV from
producing final viral proteins from precursor
proteins).
› Fusion inhibitors prevent HIV entering cells.
› Integrase inhibitors prevent HIV from inserting
HIV DNA into host’s genome.

Because HIV mutates so rapidly
treatment with a single drug will not be
successful for long.

Is there a better way?
Most successful approach has been to
use multi-drug cocktails (referred to as
HAART [Highly Active Anti-Retroviral
Treatments]
 HAART cocktails usually use three
different drugs in combination (e.g. two
reverse transcriptase inhibitors and a
protease inhibitor).

Using multi-drug cocktails sets the
evolutionary bar higher for HIV.
 To be resistant a virus particle must
possess mutations against all three drugs.
The chances of this occurring is a single
virus particle are very low.


If the same drugs were provided in
sequence to an HIV population each
time it faced a new drug it would need
only a single mutation to gain resistance,
which would then spread through the
population.

Offering drugs one at a time is
analagous to providing a stairway that
HIV must climb. Offering multiple drugs
at once requires HIV to leap from the
bottom to the top in a single bound,
which is much more difficult

Multi-drug treatments have proven very
successful in reducing viral load and
reducing mortality of patients.

However, HIV infection is not cured.
Reservoir of HIV hides in resting white
blood cells. Patients who go off HAART
therapy experience increased HIV loads.

For patients on HAART whether HIV
replication is stopped completely or not is
crucial. In some HIV appears dormant and
no replication means no evolution.

In other patients replication occurs,
although slowly. However, this allows HIV to
mutate and resistance to develop. So far,
few HAART regimens are effective for more
than 3 years.

Other downside of HAART therapy is that
many patients experience severe side
effects.

These patients have difficulties
maintaining their treatment regimen.

Because of severe side effects of HAART
therapy some doctors have advocated
“drug holidays” for their patients (i.e. to
have patients stop taking drugs for a
while). From an evolutionary perspective
does this seem like a good idea or not?

Because a drug holiday allows HIV to
replicate it is likely to be a very bad idea.

Every time HIV replicates it produces
new mutants and this increases the
chance that a resistant form of HIV will
be produced.

Where did HIV come from?

HIV similar to viruses in monkeys called
SIV (simian immunodeficiency virus).

To identify ancestry of HIV scientists have
sequenced various HIV strains and
compared them to various SIV strains.

HIV-1 is most similar to an SIV found in
chimps and HIV-2 is most similar to an SIV
found in a monkey called the sooty
mangabey.

HIV-1 occurs in three different subgroups
(called M,N and O) and each appears
closely related to a different
chimpanzee SIV strain.

Thus appears that HIV-1 jumped to
humans from chimps on at least 3
occasions.

Most likely acquired through killing and
butchering chimps and monkeys in the
“bushmeat” trade.

Sequence data from several group M
strains has been used estimate when HIV
moved from chimps to humans.

Korber et al. (2000) analyzed nucleotide
sequence data for 159 samples of HIV-1
strain M. Constructed a phylogenetic tree
showing relatedness to a common ancestor
of the 159 samples.

Extrapolating based on rates of change
of different strains suggests that
subgroup M probably infected humans
in the early 1930’s.

To summarize: our understanding of
evolutionary biology has enabled us to
understand why HIV is so hard to treat,
devise treatment methods that take
evolution into account and reconstruct
the likely history of the disease.

The process of Evolution is widely
misunderstood and most people have
only a vague understanding of the
principle mechanisms (natural selection,
genetic drift) by which it occurs.

As a result there are many
misperceptions about how evolution
occurs.

All scientific theories are backed by multiple
lines of evidence
› A theory is not just a “hunch.” All theories
provide broad, overarching explanations for
major aspects of the natural world and have
been extensively tested over time.

Other scientific theories
› Gravity
› Plate tectonics
› Germ theory

Evolutionary theory is overwhelmingly
accepted by scientists

Biologists continually discover new
information about life and the biological
world.
› All that new information fits or is understood
within the context of an evolutionary
framework , because evolutionary theory
provides a unifying framework for all biology.
Evolution deals with how life has changed
after it originated
 Other scientific fields address the origin of
life, but an understanding of evolution
especially the process of natural
selection, is relevant to discussions of life’s
origins.

Newspaper reports always seem to focus
on “missing links.” In reality, the fossil
record is very incomplete and finding a
direct ancestor of a particular organism
is unlikely.
 Available evidence strongly supports
relationships between current and past
species and fossil evidence sheds light
on how traits evolved.


The second law holds that disorder
increases in closed systems (entropy
always increases).

However, the Earth is not a closed system
because the sun provides a constant
input of energy.
Natural selection is a crucially important
mechanism of evolutionary change but
it is not the only one
 Other mechanisms include:

› Genetic drift
› Sexual selection

Evolution includes random and non-random
components
› Mutations occur randomly
› However, natural selection is completely non-
random and it results in the spread of mutations
that increase the survival and reproduction of the
organisms that possess them.

Convergent evolution also demonstrates
that evolution is non-random
› Phenotypes are predictable when environments
are similar

Evolution cannot identify or anticipate
the needs of an organism
› Mutations do not occur because they would
be adaptive in an environment
› If beneficial mutations happen to occur by
chance they may increase in frequency
through selection

Evolution is not ladder-like
› New species result from branching events
› Evolutionary patterns are bush-like not ladder-
like.

Evolution can also move from complex
to simple
› e.g. mitochondria evolved from free-living
bacteria
› Parasitic tapeworms do not possess a gut
because they live attached to the intestines
of their host and have no need to digest
their own food. They just absorb predigested
nutrients from their surroundings.

Evolution only works on inherited traits
› Acquired changes are not passed to
offspring. No matter how much you practice
a musical instrument you cannot pass that
ability on to your child.

Populations evolve; individuals do not
› Evolution results from changes in allele
frequencies that result from the success or
failure of individuals to reproduce (e.g. as a
result of natural selection or sexual selection)

Natural selection can only work with
available variation
› Constrained by physical limitations and
development

Many traits involved in trade-offs
› e.g. human brain size
› Structures may have to perform multiple
different tasks and cannot be equally good
at all of them

Evolution selects traits that are beneficial
for individuals or their genes
› Traits that are bad for individuals (or genes)
will not be selected even if they are good for
the species

Natural selection favors traits that
increase reproductive success
› Different conditions select for different traits
› Cooperative traits are beneficial under
many conditions.
› Cruelty is a human concept Nature is not
cruel. Rather Nature is pitilessly indifferent.

Natural selection favors traits that
increase reproductive success
› Can result in overexploitation of resources,
habitat destruction, the extinction of other
species and many other non-harmonious
outcomes.

All of life is adapted to the environment in
numerous ways
› Environments differ so the adaptations to
succeed in different environments differ also.
› One organism is not “superior” to another
organism just because we think it’s simpler. For
example, a jellyfish is beautifully adapted to the
role of a floating sit-and-wait predator even
though it has no brain.
› Remember all living organisms are the product
of many millions of years of evolution and it’s
hard to improve them. That’s why most
mutations are harmful.

Extinction means diversity is not stable
› More than 99% of all species that have ever
existed are extinct.
› There has and always will be constant
turnover in the diversity of life.