Natural History of HIV/AIDS
Acquired immune deficiency syndrome (AIDS)
caused by Human Immunodeficiency Virus (HIV).
Immune system attacked. Victim dies of secondary
infections.
Projected mortality by 2020 --90 million lives
Responsible for about 5% of all deaths worldwide.
The Human Immunodeficiency
Virus
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.
Cells HIV infects are critical to immune
system function
Immune system collapse leads to AIDS.
Patient vulnerable to opportunistic
infections
Why is HIV hard to treat?
Drug resistance.
AZT (azidothymidine) first HIV wonder
drug
Works by interfering with HIV’s reverse
transcriptase enzyme, which the virus uses
to transcribe its viral RNA into DNA
Drug resistance.
AZT similar to thymidine (one of 4 bases of
DNA nucleotides) but has an azide group
(N3) in place of hydroxyl group (OH).
AZT added to DNA strand prevents strand
from growing. Azide blocks attachment of
next nucleotide.
Drug resistance.
AZT successful in tests although with
serious side effects.
After only a few years patients stopped
responding to treatment.
Evolution of AZT-resistant HIV in patients
usually took only about 6 months.
How does resistant virus differ?
Reverse transcriptase gene in resistant
strains differ genetically from non-resistant
strains.
Mutations located in active site of reverse
transcriptase.
Selectively block binding of AZT
How did resistance develop?
HIV reverse transcriptase very error prone.
Half of DNA transcripts produced contain
an error (mutation).
HIV has highest mutation rate known.
There is thus VARIATION in the HIV
population in a patient.
How did resistance develop?
High mutation rate makes occurrence of
AZT-resistant mutations almost certain.
NATURAL SELECTION now starts to act
in presence of AZT
Selection in action
Presence of AZT suppresses replication of
non-resistant strains.
Resistant strains replicate and pass on their
resistance. Resistance is HERITABLE.
AZT-resistant strains replace non-resistant
strains. EVOLUTION has occurred.
Other examples of natural
selection
There are other examples of natural
selection in action in your textbook chapter
22. You should study these too.
Evidence for evolution.
1. Fossil record.
Fossils show that species have changed
over time.
Many transitional fossils that are
intermediate between extinct and
modern species are known.
Archaeopteryx
(oldest known
fossil bird)
Evidence for evolution.
2. Anatomical evidence.
(a) Homologous structures. Many
structures, often with different functions,
are made from the same ancestral parts.
E.g. human arm, cat’s forelimb, bat’s wing,
and whale’s flipper all contain the same
bones.
Homologous structures imply that
organisms that may look very dissimilar in
fact share a common ancestry.
Homology: similarity resulting from
common ancestry.
Evidence for evolution.
2. Anatomical evidence.
(b) Vestigial structures. Structures
with no current function but are
retained by the body. Imply
organisms have an evolutionary history.
Human examples?
Human vestigial structures
Coccyx (tailbone)
Appendix
Wisdom teeth
Evidence for evolution.
2. Anatomical evidence.
(c) Jerry-rigged structures
e.g. The Panda’s thumb.
In Pandas, a wrist bone is modified into
a “thumb” used to strip bamboo stalks.
Panda’s thumb not the “best possible”
solution. Natural selection has to work
with the material available.
Implies pandas not designed, but
evolved.
Evidence for evolution.
2. Anatomical evidence.
(d) Developmental homologies.
Embryos of different organisms
display primitive features
(e.g. gill slits/pharyngeal pouches,
post anal tail) during development.
“Old” instructions remain in our DNA
Evidence for evolution.
3. Molecular evidence.
All organisms share DNA/RNA as
genetic material.
Evidence for evolution.
3. Molecular evidence.
Patterns of species relatedness based on
anatomy match those derived from
molecular data.
Evidence for evolution.
4. Adaptive radiation and clusters of
species.
Many remote islands populated by
different, but closely related species.
Adaptive radiation: Ancestral colonist
arrives on island.
Absence of other species meant little
competition.
Descendents diversified to fill vacant
niches (ecological opportunities) on
the island. Speciation occurred rapidly.
Example of adaptive radiation:
Darwin’s Finches.
13 species of anatomically quite
different, but closely related finches
occur on Galapagos Islands .
In absence of competitors, Darwin’s
finches filled diverse ecological
roles.
Huge variation in beak size and diet.
Evidence for Evolution
Further evidence for evolution that relates
to Biogeography (distributions of animals
across the planet) were discussed earlier
under the heading “What Darwin observed”
during the voyage of the Beagle.
Chapter 23. The Evolution of
Populations
Remember individual organisms do not
evolve. Individuals are selected, but it is
populations that evolve.
Because evolution occurs when gene pools
change from one generation to the next,
understanding evolution require us to
understand population genetics.
Some terminology
Population: All the members of one species
living in single area.
Gene pool: the collection of genes in a
population. It includes all the alleles of all
genes in the population.
Some terminology
If all individuals in a population all have the same
allele for a particular gene that allele is said to be
fixed in the population.
If there are 2 or more alleles for a given gene in
the population then individuals may be either
homozygous or heterozygous (i.e. have two
copies of one allele or have two different alleles)
Detecting evolution in nature
Evolution is defined as changes in the structure of
gene pools from one generation to the next.
How can we tell if the gene pool changes from one
generation to the next?
We can make use of a simple calculation called the
Hardy-Weinberg Equilibrium
Hardy-Weinberg Equilibrium
Before discussing Hardy-Weinberg need to review some
basic facts about Mendelian Inheritance.
In Mendelian Inheritance alleles are shuffled each
generation into new bodies in a way similar to which cards
are shuffled into hands in different rounds of a card game.
The process of Mendelian Inheritance preserves genetic
diversity from one generation to the next. A recessive
allele may not be visible because it is hidden by the
presence of a dominant allele, but it is still present.
Hardy-Weinberg Equilibrium
The shuffling process occurs because an
individual has two copies of any given gene
(one inherited from father and one from
mother), but can put only one or the other
copy into a particular sperm or egg. E.g. for
an individual who is heterozygous Aa 50%
of sperm will contain A and 50% will
contain a.
Hardy-Weinberg Equilibrium
Individuals alleles thus go through a process
where they are sorted into gametes (sperm
or egg) which combine to form a zygote
which will one day again sort alleles into
gametes.
See Chapter 14 to review Mendelian
Inheritance
Hardy-Weinberg Equilibrium
Consider a population of 100 individuals.
This population will contain 200 copies of
any given gene because each individual has
two copies.
Gene we are interested in has two alleles A
and a.
Hardy-Weinberg Equilibrium
If 80% of the alleles in the gene pool are A and
20% are a, we can predict the genotypes in the
next generation.
Basic probability: To determine the probability of
two independent events both occurring, you
should multiply the probabilities of the individual
events together.
Hardy-Weinberg Equilibrium
Probability of an AA individual is 0.8*0.8 =
0.64
Probability of an aa individual is 0.2*0.2 =
0.04
Probability of an Aa individuals is 0.2*0.8 =
0.16, but there are two ways to produce an
Aa individual so 0.16*2= 0.32.
Note these probabilities sum to 1.
Hardy-Weinberg Equilibrium
General formula for Hardy-Weinberg is
p2 + 2pq + q2 = 1, where p is frequency of
allele 1 and q is frequency of allele 2.
p + q = 1.
Hardy-Weinberg Equilibrium
Hardy-Weinberg equilibrium can be used to
estimate allele frequencies from information
about phenotypes and genotypes.
Hardy-Weinberg Equilibrium
E.g. approx 1 in 10,000 babies are born with
phenylketonuria (PKU) (causes retardation
if diet is not kept free of amino acid
phenylalanine).
Disease due to individual being
homozygous for a recessive allele k. i.e., the
babies’ genotype is kk.
Hardy-Weinberg Equilibrium
What is frequency of k allele in population?
q2 = frequency of PKU in population = 0.0001.
q = square root of q2 or 0.01. Frequency of allele k
Therefore p the frequency of the K allele = 1 0.01 = 0.99
Frequency of carriers (heterozygotes) in
population is 2pq =
2*0.99*0.01 = 0.0198 or almost 2% of population.
Much greater than frequency of PKU.
Hardy-Weinberg Equilibrium
If a population is found to depart
significantly from Hardy-Weinberg
equilibrium this is strong evidence that
evolution is taking place.
Hardy-Weinberg Equilibrium
Conditions under which Hardy-Weinberg
equilibrium holds:
No gene flow.
Random mating.
Large population size.
No natural selection.
No mutations.
Gene flow
Movement of individuals between
populations can alter gene frequencies in
both populations.
Frequent migration may cause populations’
gene pools to converge.
Non-random mating
Mating preferentially with others that are
phenotypically similar to you [in extreme
cases inbreeding (mating with relatives)]
can prevent random mixing of genes
Homozygotes are common in inbred
populations.
Large population size
If populations are small, chance events
(genetic drift) can have a large effect on
gene frequencies.
Natural Selection
Is generally the main reason populations
will deviate from H-W equilibrium.
With natural selection certain alleles are
selected against or for and so are are rarer or
more common than would otherwise be
expected in the next generation.
Mutation
Mutation adds new genes, but generally so
slowly that H-W equilibrium not affected.
However, mutation and sexual
recombination ultimately responsible for the
variation that natural selection depends on.
Mutations
Mutations are randomly occurring changes in the
DNA.
Only mutations that occur in cell lines that
produce gametes can be passed on.
Simplest mutation is a point mutation in which
one base is changed or a base is inserted or
deleted.
Mutations
Changing a base may have no effect if the base
change does not change the amino acid coded for
or if the change occurs in a non-coding section of
the gene.
However, some changes alter the amino acid
coded for and hence the protein produced (e.g. as
occurs in sickle cell anemia), which can have
severe effects.
Insertion/deletion mutations
In insertion/deletion mutations a base is
added or deleted, which because bases are
read in groups of three shifts the “reading
frame” so that all sequences after the
mutation are misread, being off by one base.
This almost always produces a nonfunctional protein
Mutations that alter gene number or
sequence
Gene duplication is an important source of
variation.
In gene duplication a section of DNA may be
copied and inserted elsewhere in the genome.
Often these cause major problems, but sometimes
they do not and the overall number of genes is
increased. And the new genes can take on novel
functions through mutation and selection
Mutations that alter gene number or
sequence
Humans have about 1,000 olfactory
receptor genes and mice about 1,300. These
appear all to have been derived from a
single ancestral gene.
In humans about 60% of these are turned
off, but in mice only about 20% are turned
off.
Sexual Recombination
In the process of meiosis alleles are
reshuffled as parental chromosomes
exchange portions.
This process produces new combinations of
alleles. In addition, the combining of sperm
and egg also produces new combinations of
alleles.
How populations’ gene pools are
altered
Natural Selection: as discussed selection
for or against allele can cause its frequency
to change quickly from one generation to
the next.
However, natural selection is not the only
way gene frequencies can change. Chance
can also play a role.
Genetic drift
Fluctuations in gene frequencies that result
from chance are referred to as genetic drift.
Chance effects are strongest when
populations are small. In a small population
it is easy for alleles to be lost or become
fixed as a result of chance events.
Genetic Drift
Genetic drift is most likely to affect
populations after events that greatly reduce
population size.
Two of the most common are Bottleneck
Events and Founder Events
Bottleneck Effect
The bottleneck effect occurs when some disaster
causes a dramatic reduction in population size.
As a result, by chance certain alleles may be
overrepresented in the survivors, while others are
underrepresented or eliminated. Genetic drift
while the population is small may lead to further
loss or fixation of alleles.
Bottleneck Effect
Humans have been responsible for many
bottlenecks by driving species close to extinction.
The Northern Elephant seal population for
example was reduced to about 20 individuals in
the 1890’s. Population now >30,000, but an
examination of 24 genes found no variation, i.e.
there was only one allele. Southern Elephant
Seals in contrast show lots of genetic variation.
23.8
Founder Effect
When populations are founded by only a
few individuals (as island communities
often are) the gene pool is unlikely to be as
diverse as the source pool from which it
was derived.
Founder Effect
Founder effect coupled with inbreeding explains
the high incidences of certain recessive diseases
among humans in many isolated island
communities.
For example, polydactylism (having extra fingers)
is quite common among the Amish and retinitis
pigmentosa a progressive from of blindness is
common among the residents of Tristan da Cunha.
Natural Selection the primary
mechanism of adaptive evolution
Terms such as “survival of the fittest” and
“struggle for existence” do not necessarily mean
there is actual fighting for resources.
Competition is generally more subtle and success
in producing offspring and thus contributing genes
to the next generation (i.e. fitness) may depend on
differences in ability to gather food, hide from
predators, or tolerate extreme temperatures, which
all may enhance survival and ultimately
reproduction
Natural Selection the primary
mechanism of adaptive evolution
Three major forms of natural selection:
Directional
Disruptive
Stabilizing
Directional Selection
Favors one extreme in the population
Average value in population moves in that
direction
E.g. Selection for darker fur color in an area
where the background rocks are dark
Disruptive selection
Intermediate forms are selected against.
Extremes are favored
E.g. Pipilo dardanus butterflies. Different
forms of the species mimic the coloration of
different distasteful butterflies.
Crosses between forms are poor mimics and
so are selected against by being eaten by
birds.
Stabilizing Selection
Commonest form
Extreme forms are selected against
Birth weights in human babies. Highest
survival is at intermediate birth weights.
Babies that are too large cannot fit through
the birth canal, babies that are born too
small are not well developed enough to
survive
Important points about evolution
and natural selection
No directionality
Adaptation equips organisms for current
conditions only.
There is no foresight. Natural selection
cannot plan ahead.
Important points about evolution
and natural selection
The fundamental unit of natural selection is
the gene.
Only genes are passed on from one
generation to the next.
Important points about evolution
and natural selection
Nothing in nature happens for “the good of
the species.”
Genes that sacrifice themselves would
disappear from the population.
Important points about evolution
and natural selection
Organs must be useful at all stages of their
evolutionary history
Structures cannot pass through intermediate
stages where they make an organism less
well adapted.
Important points about evolution
and natural selection
Evolutionary success is measured relative to
the competition.
If you and I are being chased by a lion you
don’t need to outrun the lion, you need to
outrun me.
Important points about evolution
and natural selection
Natural selection cannot fashion perfect
organisms for several reasons
1. Evolution is limited by historical
constraints. Birds cannot run around on
four legs because their forelimbs have
evolved into wings.
Important points about evolution
and natural selection
Natural selection cannot fashion perfect
organisms for several reasons
2. Adaptations are often compromises.
A puffin can fly and use its wings to swim
underwater, but the shape and size of the
wing is a compromise between the demands
of flight and swimming.
Important points about evolution
and natural selection
Natural selection cannot fashion perfect
organisms for several reasons
3. Selection can only make use of the
material that is available. New alleles do
not arise on demand.