P1252109113vFfbu - PowerPoint PPT Presentation

Title: P1252109113vFfbu


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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.

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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.

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• Cells HIV infects are critical to immune system
  function
• Immune system collapse leads to AIDS.
• Patient vulnerable to opportunistic infections

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Why is HIV hard to treat?Drug resistance.

• AZT (azidothymidine) first HIV wonder drug
• Works by interfering with HIVs reverse
  transcriptase enzyme, which the virus uses to
  transcribe its viral RNA into DNA

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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.

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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.

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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

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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.

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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

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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.

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Other examples of natural selection

• There are other examples of natural selection in
  action in your textbook chapter 22. You should
  study these too.

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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.
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Archaeopteryx (oldest known fossil bird)
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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, cats forelimb,
bats wing, and whales flipper all contain the
same bones.
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• Homologous structures imply that organisms that
  may look very dissimilar in fact share a common
  ancestry.
• Homology similarity resulting from common
  ancestry.

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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?
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Human vestigial structures Coccyx
(tailbone) Appendix Wisdom teeth
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Evidence for evolution.
2. Anatomical evidence.
(c) Jerry-rigged structures e.g. The Pandas
thumb.
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In Pandas, a wrist bone is modified into a
thumb used to strip bamboo stalks. Pandas
thumb not the best possible solution. Natural
selection has to work with the material
available. Implies pandas not designed,
but evolved.
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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
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Evidence for evolution.
3. Molecular evidence. All organisms share
DNA/RNA as genetic material.
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Evidence for evolution.
3. Molecular evidence.
Patterns of species relatedness based on anatomy
match those derived from molecular data.
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Evidence for evolution. 4. Adaptive radiation
and clusters of species. Many remote islands
populated by different, but closely related
species.
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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.
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Example of adaptive radiation Darwins
Finches. 13 species of anatomically quite
different, but closely related finches occur
on Galapagos Islands .
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In absence of competitors, Darwins finches
filled diverse ecological roles. Huge variation
in beak size and diet.
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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.

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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.

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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.

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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)

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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

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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.

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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.

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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

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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.

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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.

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Hardy-Weinberg Equilibrium

• Probability of an AA individual is 0.80.8 0.64
• Probability of an aa individual is 0.20.2 0.04
• Probability of an Aa individuals is 0.20.8
  0.16, but there are two ways to produce an Aa
  individual so 0.162 0.32.
• Note these probabilities sum to 1.

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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.

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Hardy-Weinberg Equilibrium

• Hardy-Weinberg equilibrium can be used to
  estimate allele frequencies from information
  about phenotypes and genotypes.

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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.

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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
• 20.990.01 0.0198 or almost 2 of population.
  Much greater than frequency of PKU.

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Hardy-Weinberg Equilibrium

• If a population is found to depart significantly
  from Hardy-Weinberg equilibrium this is strong
  evidence that evolution is taking place.

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Hardy-Weinberg Equilibrium

• Conditions under which Hardy-Weinberg equilibrium
  holds
• No gene flow.
• Random mating.
• Large population size.
• No natural selection.
• No mutations.

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Gene flow

• Movement of individuals between populations can
  alter gene frequencies in both populations.
• Frequent migration may cause populations gene
  pools to converge.

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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.

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Large population size

• If populations are small, chance events (genetic
  drift) can have a large effect on gene
  frequencies.

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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.

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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.

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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.

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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.

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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 non-functional
  protein

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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

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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.

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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.

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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.

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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.

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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

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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.

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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
  1890s. Population now gt30,000, 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.

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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.

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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.

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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

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Natural Selection the primary mechanism of
adaptive evolution

• Three major forms of natural selection
• Directional
• Disruptive
• Stabilizing

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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

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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.

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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

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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.

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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.

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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.

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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.

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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 dont
  need to outrun the lion, you need to outrun me.

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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.

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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.

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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.