
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?”

Whales: mammals gone to sea
 Viruses: the deadly escape artists


Whales share synapomorphies (shared
derived characters) with mammals
› Mammary glands
› Three middle ear bones
› Single jaw bone (dentary)
› Hair (in developing embryos)

Similarities with fish [streamlining, fins]
arose through convergent evolution

Whales are aquatic mammals that
evolved from terrestrial ancestors
through the process of natural selection
by which individuals that possessed traits
that best fitted them to life in water left
behind the most offspring.

The evolution of whales is well
documented by fossil discoveries.

Modern whales have peg-like teeth or
baleen for feeding. Early fossil whales
such as Dorudon (40 mya) however had
more complex teeth that were similar to
those of contemporary terrestrial
mammals.

Dorudon and modern whales share
numerous features of the skull in
common, including a distinctively thickwalled ectotympanic bone.

The same distinctive bone is found in
Pakicetus a terrestrial wolf-like animal
from 50 mya.

Pakicetus also possesses a distinctive
ankle bone called the astragalus. In
Pakicetus it has a double-pulley like
morphology and this structure is found
only in artiodactyls (hoofed mammals
such as cows, pigs and deer).
• Shape of astragalus connects to artiodactyls

These and other fossil discoveries have
enabled biologists to construct a
phylogentic tree (a tree of branching
relationships) that depicts the
evolutionary history of the group.
Whales: mammals gone to sea
 Viruses: the deadly escape artists


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).
WHO estimate in 2012 -- 35.3 million
people living with HIV/AIDS
 In 2012 1.3 million people died of AIDS

HIV 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 and three enzymes:

Reverse transcriptase

Integrase

Protease

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.

Why would that be?

Immune system destroys virus particles in
bloodstream and cells infected with
virus.

Unfortunately, HIV infects cells critical to
immune system function.

HIV invades immune system cells called
helper T cells.

When a helper T cell is activated (by
encountering an antigen [something
foreign], it divides into memory T cells
and effector T cells.

Memory T cells are :
› long-lived
› generate an immune response quickly if the
same foreign protein is encountered again.

Effector T cells attack HIV by:
1. Producing chemokines that stimulate B cells to
produce antibodies to the virus.
2. Stimulating macrophages to ingest cells
infected with the virus.
3. Stimulating killer T cells to destroy infected cells
displaying viral proteins.
First round of infection with HIV reduces
the pool of CD4 Helper T cells .
 Loss of CD4 helper T cells cells is bad, but
immune system now ready to recognize
HIV.
 What’s the problem?

Virus mutates and the proteins on its
outer surface (gp120 and gp41) change.
 The new surface proteins are not
recognized by the immune systems
memory cells.
 Mutants evade immune system and
begin new round of infection


Each cycle of mutation and infection
reduces the numbers of helper T cells
because they are infected by virus and
destroyed.

Over time the body’s supply of helper T cells
becomes exhausted and the immune
system collapses.
AZT (azidothymidine) -- first HIV wonder
drug
 AZT interferes with HIV’s reverse
transcriptase, [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.


AZT successful in tests 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 of HIV differs from nonresistant strains.
 Mutations are located in active site of
reverse transcriptase.
 These changes prevent AZT binding to
DNA chain but allow other nucleotides
to bind.

HIV reverse transcriptase very error
prone.
 About half of all DNA transcripts
produced contain an error (mutation).
 There is thus VARIATION in the HIV
population in a patient.


HIV’s 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.
 There is thus DIFFERENTIAL REPRODUCTIVE
SUCCESS of HIV strains. Resistant strains
produce more offspring than nonresistant.


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.
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.


Many different 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.

We know treatment with a single drug
will not be successful for long.

Why?

Multi-drug cocktails (referred to as
HAART [Highly Active Anti-Retroviral
Treatments] have proven successful.

HAART cocktails combine different drugs
(e.g. two reverse transcriptase inhibitors
and a protease inhibitor).

Why do HAART cocktails work?
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.

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.

A downside of HAART therapy is that
many patients experience severe side
effects.

Because of severe side effects 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?

Where did HIV come from?

HIV similar to a virus in monkeys and apes
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
http://animals.nationalgeographic.co
m/animals/mammals/chimpanzee/

HIV-2 is most similar to an SIV found in a
monkey called the sooty mangabey.
http://pin.primate.wisc.edu/factsheets/
entry/sooty_mangabey/cons

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 to estimate when HIV
moved from chimps to humans.

Korber et al. (2000) analyzed nucleotide
sequence data for 159 samples of HIV-1
strain M. Extrapolating from 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:
 1. understand why HIV is so hard to treat
2. devise treatment methods that take
evolution into account and
3. reconstruct the likely history of the
disease.


The process of Evolution is widely
misunderstood and many
misperceptions are common.

All scientific theories are backed by
multiple lines of evidence
› A theory is not just a “hunch.”
› A theory is a broad, overarching explanation
for a major aspect of the natural world that
has been extensively tested over time.
› Other scientific theories?

Other scientific theories
› Gravity
› Plate tectonics
› Germ theory
› Atomic theory of matter

The second law holds that disorder
increases in closed systems (entropy always
increases).

Some creationists argue that because
evolution often results in the development
of more complex forms from less complex
that the first law is violated.

What’s the flaw in the argument?

The Earth is not a closed system.

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
› But, natural selection is completely non-random.
› Selection favors mutations that increase the
survival and reproduction of the organisms that
possess them.
› Selection allows beneficial changes to
accumulate from generation to generation.

Convergent evolution also demonstrates
that evolution is non-random
› Similar body forms evolve when
environments are similar.
› (E.g. fish, whales, seals and sharks all have
streamlined bodies that easily move through
water).

Evolution cannot anticipate the needs of
an organism
› Mutations do not occur because they would
be useful.
› 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 have no digestive
system.

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 favors traits that
increase reproductive success
› Cooperative traits are beneficial under
many conditions.
› Cruelty is a human concept Nature is not
cruel. Rather Nature is pitilessly indifferent.

“Higher” and “lower” are just human
judgment calls. All organisms are well
adapted to the environment

Remember: All living organisms are the product
of millions of years of selection and it’s hard to
improve them.

That’s why most mutations are harmful.

Constraints and trade-offs limit how well
organisms can adapt.

Evolution selects traits that are beneficial
for individuals or their genes
› Traits that are bad for individuals (or genes)
will not be selected for even if they are good
for the species as a whole.