EVOLUTION

1) Darwin: Decent with modification

2) Change in the genetic

Pseudogene (def)

• A sequence of DNA similar to a functional gene but nonfunctional (vestigial structures)

• (COMMON IN HUMAN GENOME)

Where did pseudogenes come from?

1. Mutation that causes an early stop codon

2. Other loss-of-function mutations

Examples of pseudogene

Example 1: hemoglobin ψα

Example 2: Olfactory receptor (OR) genes

Example: soapberry bug

• Change through time
• To penetrate thick fruit -> long beak
• Thin fruit -> short beak
• soapberry bug beak length decreased in response to introduced food source (thin fruits)

Fossil (define)

any trace of an organism that lived in the past.

extinction

• complete elimination of all individuals of a species from the face of the Earth 

• common occurrence 99%, evidence from fossil record.

Law of Succession

• Fossil types are succeeded in the same geographical area by similar fossil or/and extant species
• close relationship between fossils and extant species in geographical area

Law of Succession (2 Examples)

• Example 1: similarity between fossils of marsupials in Australia and the marsupials presently living there.
• Example 2: (1) South America today, armadillo (2) S.A. fossil: giant mammals with plates of armor

fossil record; Law of Succession

• Ancestor → Transitional form → Descendant
• Example: Reptile → Archaeopteryx → Bird

Taxon

any named group of organisms, such as species, genus, or family

Sister taxa

two taxa share a more recent common ancestor with each other than either does with any other species on the tree

Homology

similarity between species that results from inheritance of traits from a common ancestor

• (likeness attributed to shared ancestry)

3 types of homology

1. Structural and morphological homology
2. Developmental homology
3. Molecular homology

Structural Homology

• Different functions, same sequence and arrangement of bones.
• Example 1: vertebrate forelimbs
• (human, mole, horse dolphin bat) similar bone pattern

Analogy

• Similarity due to common functions;
• Not a trait inherited from a common ancestor;
• Example: shark, whale, submarine

Developmental homology

Example: vertebrate embryo

Molecular homology (1)

• Conservation of the genetic code
• Example: DNA/RNA components:
• AGCT/U
•  Codons conserved;
•  All organisms inherited their genetic code from a common ancestor

Molecular homology (2) shared genetic flaw

• Shared flaw suggests common ancestry
• Example: a genetic flaw that humans share with chimps
• genetic flaw caused by CMT1A proximal repeat
• absent in gorillas, orangutans, and other monkeys
• »human and chimps inherited the proximal repeat from a recent common ancestor

Artificial Selection (definition)

selective breeding of domesticated plants and domesticated animals to encourage the occurrence of desirable traits.

The effect of Artificial Selection

(1) Desirable traits: two strains are artificially selected

(a) broiler strain: for meat production

(b) layer strain: for egg production

(2) Unconscious selection: However, in the search for desirable traits, several other traits may be and often are unconsciously selected.

(3) Genetic trade-off In broiler chicken:

Desired trait: increased body size

Unconscious selection: increased gut size and intestine mass Genetic trade-off: the decrease in brain size and leg mass

Natural SelectionDarwin’s Four Postulates

1. Individuals within species are variable
2. Some of these variations are passed to offspring (Heritable)
3. In every generation, some individuals are more successful at surviving and reproducing than others (Fitness varies)
4. The survival and reproduction of individuals are not random. Those individuals who are better at surviving and reproducing are naturally selected -- gradual change in populations over time

Darwinian Fitness:

the ability of an individual to survive and reproduce in its environment

Adaptation

a trait of an organism that increases its fitness relative to individuals without the trait

AZT resistance as an example of evolution by Natural Selection

• Postulate 1: mutations by reverse transcriptase produce variant HIV molecules: susceptible, partially resistant, resistant
• Postulate 2: mutants are passed to ‘offspring’ of resistant genotypes - heritable.
• Postulate 3: mutants differ in enzyme function, differential survival in AZT environment
• Postulate 4: The AZT- resistant mutants are naturally selected, resulting in a population of mostly AZT-resistant viruses

Snapdragon

1. Postulate 1 (variation):
• White vs. yellow
2. Postulate 2 (heritable):
• Color controlled by gene S (Mendelian)
• White (dominant): SS (25%), Ss (50%)
• Yellow (recessive): ss (25%)
3. Test postulates 3 and 4 (individuals vary in their fitness):
• White plants, more successful,  attracted twice as many bee
4. Survival and reproduction Nonrandom?
• Because plants with white flowers are more successful at reproduction, they occupy larger fraction of the population in the next generation

Evidence for evolution

Change through time Common ancestry

Microevolution

• small scale evolutionary changes

• changes in gene frequencies and trait distributions that occur within populations and species

Macroevolution

• Large scale evolutionary changes
• Evolution on a species level (speciation and extinction) and at higher taxonomic classifications (appearance and disappearance of genera, families, orders, etc.)
• Typically refers to the evolutionary differences among populations
• Usually in morphology

Evidence of Evolution from living species:

Vestigial (rudimentary) structures

Vestigial Structures

• a functionless or rudimentary version of a body part that has an important function in other closely allied species
• Structures with no apparent nor predictable function (unusable organs)

EX of Vestigial Structures

• Eye sockets on Blind Cave Fish
• Rudiments of pelvis and hind limbs in snakes
• Wings on birds that do not fly?
• Flower in self-pollinating plant?

EX of Vestigial Structures in Humans

• Ear-wiggling muscles
• Tail present in human and all vertebrate embryos.
• Appendix Structure
• Wisdom teeth

Rudimentary organs in early embryo later lost (Example)

Dolphin embryo with well-developed early hindlimb bud. (vestigal structure) 

How does decent explain vestigial structures?

• The ancestor had an organ that was fully developed/functional.
• Each feature in an organism tends to be inherited, even if they are not used by descendants

Vestigial experiment:

• Experiment in Mexican tetra fish
• two populations:
• -cave population (vestigial eye socket)
• -surface dwelling fish (normal eyes)
• (1) surface × cave → offspring (small eyes) (trait is inherited)
• (2) transplant lens tissue of surface fish to cave fish → cave fish grow eyes (note cave fish has a degenerate optical nerve and retina)
• Conclusion: Blind cave populations are descendants from eyed, surface dwelling populations; They lost their eyes only recently

Vestigial features are of great importance in ....

classification (which thereby reflect inheritance)

two mechanism for vestigial structures

• Mechanism 1: “disuse”
• Mechanism 2: Natural Selection
• organ useful under some circumstances may be injurious under others
• EX: Beetles on small islands:
• forewings are transformed into hard shells, called elytra. b/c windy island & flying beetles get blown into the sea (advantage= no wings)

Definition: Molecular vestigial structures

• A sequence of DNA similar to a functional gene but nonfunctional
• probably the remnant of a once
• functional gene that accumulated mutations.

Olfactory receptor pseudogenes

• humans> 1000 OR genes, 70% pseudogenes
• reduced sense of smell b/c with loss of functional genes
• extreme EX: dolphins,
• many OR genes, all ψ
• descendant of land mammals that no longer has need to smell volatile odorants

example of extinct animals

• Irish elk, the largest deer ever lived It was extinct species, a relative of living species.
• evolved during the glacial periods
• Unable to adapt to the subarctic conditions of the last glaciations

Evidence of Change Through Time-

Evidence from the fossil record

(1) Fact of Extinction

(2) Law of Succession

(3) Transitional forms

Molecular homology (2 types)

(1) Conservation of the genetic code

(2) shared genetic flaw

Artificial Selection is....

The success of artificial selection is a strong proof that selection is an effective evolutionary process.

Selection vs. Evolution (and example)

• Selection can lead to new characteristics by changing functions of existing traits
• the Panda’s thumb

Preadaptation

a trait that changes due to natural selection and acquires a new function.

Natural selection is NOT perfect

• Natural selection results in adaptation, not perfection
• Natural selection does not optimize all of the traits involved
• Trade-offs
• HIV, host longevity vs transmission rate

Fitness is not circular

• Fitness is testable
• Research can determine why certain nonrandom groups are favored
• Fitness can be measured by counting offspring, observing which individuals survive selection events

Nucleotide

• A 5-carbon sugar
• Phosphate group
• Nitrogen-containing base

Purine

Adenine (A)

Guanine (G)

Pyrimidine & paiting

Cytosine (C)

Thymine (T)

AT / GC

Codon

triplet of DNA bases that specifies an amino acid.

Genetic code

• Genetic code is highly redundant
• the same aa can be specified by more than 1 codon
• 64 codon, 20 aa.

DNA forms a template for its synthesis

DNA polymerase: DNA replication

Allele

versions of the same gene that differ in their base sequence

Mutation

a change in the base sequence of DNA

Point mutation

a change that alters a single point in the base sequence of a gene

Causes of Point mutations

• Errors during DNA synthesis (assembly and proofreading)
• Errors during repair of DNA damage

Point mutation have can be classified two ways:

I. Transition/Transversion

II. Replacement

(nonsynonymous) substitution/Silent

(synonymous) substitution

Transition

• type of point mutation
• purine ↔purine
• pyrimidine ↔ pyrimidine

Transversion

• type of point mutation
• purine ↔ pyrimidine

transition:transversion ≥

2: 1 b/c Transitions cause much less disruption in the DNA helix

Replacement (nonsynonymous) substitution

• Changes the amino acid specified by mRNA
• Example: Sickle cell anemia

Silent (synonymous) substitution

• No change in amino acid identity
• redundancy in the genetic code

Loss of function mutations (2)

• Insertion and deletion
• Often cause frame-shift mutation
• Nonsense mutation
• (stop codon)

Categories of chromosome changes

1. Those that affect the structure of the chromosome

-Inversion

-translocation

2. Those that affect the number of chromosomes

-polyploidy

Inversion (definition)

a region of DNA that has been flipped, so that the genes are in reverse order

Inversion (consequences)

• lessons frequency of crossing-over
• Genes inside tend to be inherited as a unit (supergene in linkage)
• important mutation type –
• they affect a group of alleles.
• (common in drosophilia)

Polyploidy (def)

Changes in chromosome number

Polyploidy mechanism

• errors in meiosis from diploid gametes
• Direct route: diploid gametes yield tetraploid offspring, which can self fertilize

Polyploidy (example & consequences) 

• Triploid (3N) – 3 sets of chromosomes
• Tetraploid (4N) – 4 sets of chromosomes
• Polyploid individuals are usually genetically isolated from parents.
• common in plants

Why polyploidy is important source of variation?

• produces hundreds/thousands of duplicated gene (genome duplication!)
• More important, source of new species!
• Population of polyploid individuals are often isolated from their parental species
• EX: 4n × 2n → 3n (triploid, low fertility!)

Measure genetic variation

• Wild type (+, wt) vs. mutants
• Natural populations have extensive genetic variation

Polymorphic locus

more than one allele exists at a particular locus

Polymorphism is common

Between 1/3 and ½ of all coding loci are polymorphic

genetic diversity (examples or why)

Polymorphic locus (common)

Mutation (definition)

alteration in the genetic material

importance of Mutation

• Mutation is the ultimate source of genetic variation
• Source of new alleles (nature and rate of mutations)

Determine genotypes (2ways)

1. From phenotype (Co-dominant alleles)

2. From gel electrophoresis

gel electrophoresis

-Gelatin-like material

-electric field

-Separate molecules by size, mass, and electric charge

Determine human CCR5 genotypes

• 2 alleles:
• +
• Δ32
• -3 genotypes &  response to HIV infection
• +/+: susceptible
• +/Δ32: susceptible, slow progress to AIDS
• Δ32/Δ32: resistant

Mutation leads to new allele

New allele can lead to new protein → phenotype

• (1) Darwin’s –Descent with modification
• (2) Textbook – Change in the genetic composition of a population through time, that is, across generations

1. Acquired –
•  not hereditary/ develops  from contact with (HIV).
2. Immunodeficiency –
• weakening of the immune system.
3. Syndrome –
•  group of symptoms that collectively indicate or characterize a disease. For AIDS:  co-infections /cancers, & a decrease in the # of CD4 cells 

• HIV has so far infected >65 million people;
• 25 million died.
• primarily in developing countries
• >25 million in sub-Saharan Africa (average 7.2%)
• Western Europe & Canada: 0.3%
• US 0.6%

• HIV transmitted by bodily fluid In Africa and India
• Transmitted primarily through heterosexual intercourse
• Affects men and women equally.
• In the US and Europe
• Mainly  homosexual men and intravenous drug users

1. Reverse Transcriptase

2. Integrase

3. Protease

4. RNA genome (2 copies)

5. gp120 (surface protein)

6. gp41 (anchor protein for gp 120)

1.viron (HIV's extracellular form)encounters host cell

2. gp 120 binds to CD4 and coreceptor on host

3. genome, reverse transcriptase, and integrase, and protein enter CD4 cell

4. RT syntesizes HIV DNA from RNA template

5. Integrase splices HIV DNA into host genome

6. HIV DNA transcribed to HIV mRNA by the host cell's RNA polymerase

7. HIV mRNA is translated to HIV precursor protein by host cell's ribosomes

8. Protease cleaves precursors into mature viral proteins

9. New generations of virions assembles inside host cell

10. New virions bud from host cell's membrane

-surface protein

- binds to CD4 and coreceptor on host cell

1. diploid RNA genome
2. gp120 (envelop) -- Vaccine design
3. Reverse transcriptase, RT (error-prone) -- drug design
4. Integrase
5. protease

1) HIV destroys CD4 helper T cells

• immune response impaired normal: 800-1000 cells/mm3
• AIDS: <200 cells/mm3

(2) HIV kills people indirectly by weakening the immune system, allowing opportunistic infections.

1. Acute

(sharp drop in CD4T count & sharp incline in Viral load)

2. Chronic- 9 years

(slow decline CD4T count& incline Viral load)

3. AIDS

(sharp decline CD4T count& inclineViral load)

1. Inhibit HIV development and growth
2. Inhibit HIV invasion/infection

• AZT is a nucleotide analog (thymidine, T)
• incorporated into new DNA by viral-specific enzyme: reverse transcriptase
• Reverse transcriptase does not recognize the difference between AZT and T
• AZT halts viral DNA replication

• initially very successful but quickly saw resistance
• treatment
• 1.Mutation occurs in the active site of reverse transcriptase
• 2.AZT no longer incorporated in new viral DNA. Normal T incorporated preferentially
• 3.See the same mutation in different patients

• Reverse Transcriptase is ERROR-prone
• No error correction
•  >50% of the viral DNA transcripts have at least one mistake

• No enzyme is perfect.
• Rates of polymerase fidelity vary.
• Many mechanisms of error correction
• Other sources of mutations: toxins, radiation, chemicals, etc

• It does NOT.
• There is NO conscious manipulation
• Random mutation occurs
• Advantageous variants are selected
• This is Evolution by Natural Selection

• Same AZT treatment
• Many ways to obtain an AZT resistant phenotype (protein structure/function)
• Large population size leads to many different mutations
• Drug resistance only conferred by a few alleles

• mutations by reverse transcriptase produce variant HIV molecules:
• susceptible, partially resistant, resistant
• mutants differ in enzyme function
• differential survival in AZT environment
• mutants are passed to ‘offspring’ of resistant genotypes - heritable.
• The AZT- resistant mutants outgrow the non-resistant viruses, resulting in a population of mostly AZT-resistant viruses

• There is VARIATION among individuals
• Some individuals are better able to SURVIVE and REPRODUCE than others (better FITNESS)
• The offspring of those individuals make up more and more of the following generations (HERITABLE).
• The AZT- resistant mutants outgrow the non-resistant viruses, resulting in a population of mostly AZT-resistant viruses

• resistance is costly (slow growth)
• a Trade-off
• How well do resistant viruses do when there is no drug present?
• A gradual shift in the viral population backward susceptible forms. (back-mutation).

• No.
• AZT: selection favors resistant (mutant) virus
• No AZT: selection favors susceptible (nonmutant) virus

• Organisms are constrained in a variety of ways.
• Natural selection CANNOT optimize every aspect of a life cycle.
1. Relative fitness
2. Costs and Benefits
3. Trade-off

(1) short-sighted evolution

After it kills the host, the virions inside human die too.

(2) Selection at the transmission level

• Human immunie system attack HIV
• Antibodies, Killer T-cells
• recognize and bind to epitopes (gp120, gp41)
• only target the viruses it has learned to recognize

• high mutation rate
•  creates genetically variable swarm
• (error-prone)
•  may be an adaptation to produce novel epitopes to escape detection
• (8% difference in genetic distance)

1. Recognizes/ targets epitopes from a particular HIV variant
2. Some  epitopes on new mutants  not recognized
• these can survive and reproduce
3.  Immune system mounts new response
4. but... each generation of HIV replication creates new mutant
• immune system chases a moving target.

1. HIV evolves novel epitopes that host is not capable of attacking
2. Immune system is exhausted 
• (CD4 helper cells drop precipitously)

• the rapid evolution of HIV population also hastens the extinction of its own distinction (Host killing)
• (natural selection is an automatic process
• “sees” the present, not the future)

Short-sighted evolution

Example:

and why example is shortsighted

• coreceptor switching:
• Early stage: selection favors normal HIV
•  uses human CCR5
• later, selection favors mutant X4 HIV strain
•  uses CXCR4
• (coreceptor switch is the result of natural selection).
• Why shortsighted?
• X4 virus is not transmitted (extinction!)
• X4 virus hasten the collapse of human immune system.

• CXCR4 = gp120 mutant (X4 virion)
• Early stage
• Divide less often
• Late stage
• ((Divide more rapidly! 00))

• Lethal strain becomes predominant.
• Virus enjoys the short-term advantage in survival and reproduction.

• 1st level of selection: ability to survive and reproduce within a host
• 2nd level of selection: transmission ability (from host to host)

• Example
• attenuated HIV strain: Sydney Bloodbank Cohort (SBBC)
• ATTENUATED –
• slow progress >15 yrs, compared ≈ 8 yrs
•  or Asymptomic

• has short-sighted evolution, but
• uses CXCR4 coreceptor
• mutation (deletion) in Nef gene
• Mutant SBBC strain:
• low attachment, low viral load, low damage to the host. -
• weak and benign strain

• Encodes 27kd protein
• Functions: enhance viral infectivity/pathogenicity
• helps virus attachment and entry into host cells
• boosts viral replication
• downregulates CD4 expression of host (immune evasion of HIV)

1. SBBC strain (nef mutant)
• Seldom transmitted
• (because of low rate of attachment/entry).
2. HIV-2
• Slower progression to AIDS
• Less damaging to hosts
• low transmission rate
• mainly found in West Africa.

• virulence increases when the ease/rapidity of transmission increases
• (1) high transmission rate ↔ high virulence
• (2) low transmission rate ↔ low virulence
• Selection favors strains that are transmitted at higher rate from host to host (which are often more virulent).

• host longevity vs transmission rate
• “host-killing” strategy  successful strategy if:
•  HIVreplicates rapidly
•  transmits easily to new host
•  and has a very large population of hosts

• Yes.
• People resistant to infection
• People are infected, but do not progress to AIDS for a long time

• Mutations in human helper T-cell coreceptor
• CCR5-CCR5: coreceptor required for HIV to enter the cells.
• They associate with CD4 to form a functional receptor complex
• Hypothesis: A defect in CCR5 coreceptors protect individuals from infection and/or progression.
• Major mutation: 32 nucleotides deletion CCR Δ-d32

• Δ32 allele is common in northern Europe (9%)
• hypothesis 1: natural selection favors Δ32 allele
•  immunity to another pathogen (bubonic plague or smallpox)
• hypothesis 2: genetic drift
• (Viking raid)

(1) Groups are related by descent from common ancestor

(2) Changes in characteristics occur over time

(3) Distance proportional to amount of difference

Origin of HIV

Origins of HIV 2

• Other primates  infected SIV (Simian Immunodeficiency Virus)
•  Conclusion: HIV-1 and HIV-2 are most closely related to different SIV rather than each other.
• HIV-2 originated from sooty mangabeys (in west Africa)
• HIV-1 transmitted to human from chimpanzees multiple times
• HIV-1 has evolved multiple times