A bargain The one minute responses asked for solutions to

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					A bargain

 The one-minute responses asked for solutions to practice problems

 I'll make a bargain:
  {   I'll provide solutions
  {   You promise not to skip doing the problem in class!
Monday's practice problem


 HIV-1 virus has a mutation rate up to 0.001 per base per generation

 Assume 100 critical bp in the env gene This makes the chance of a
  gene-damaging mutation  = 0:001x100 = 0:1

 As before, a reverse mutation has to hit the same base and restore its
  original state Chance of hitting the same base is 0.001. Only 1/3 of
  hits will restore the right nucleotide, so  = 0:001 £ 1=3 = 0:0003

 What is   pA (frequency of healthy allele) after 1 generation? It started
  at 1.0, but (approximately) 10% mutate, so 0.9. Back mutation does
  not matter in this generation as there are no mutant copies available
  to back-mutate.

 What is the equilibrium         
                            pA?  + = 0:003
 What would happen to this gene if it were not under selection? It would
  deteriorate fast, losing nearly 10% of copies in the rst generation
Mutation rate issues

 Please note the many possible units:
  {   Mutations per base versus per locus (gene)
  {   Mutations per year versus per generation

 For most evolutionary purposes we focus on germ line mutation

 In some organisms somatic mutation is equally important evolutionarily
Mutation rates in perspective

 Human genome has 6x109 bp.

 Point mutation rate around 1x10 9 per bp per generation

 Human population around 7 billion

 Every point mutation compatible with life exists somewhere

 Every human has several new point mutations
Mutation rates in perspective

 Most of these mutations are not in genes, and have little to no eect

 Many of the remaining ones are silent

 Most of the coding mutations are harmful, but the majority of those are
  recessive (a potential problem for your ospring, not for you)

 New benecial mutations are rare, though very important

 Very dierent from Hollywood image of \mutants"
Outline{Dominance and its implications

1.   Some useful terms


2.   What makes one allele dominant over another?


3.   Allelic series


4.   Codominance and incomplete dominance


5.   Dominance is not superiority!


6.   Overdominance


7.   Underdominance
Some useful terms

 Genotype { the alleles present in an organism

 Phenotype { the traits shown by an organism

 Homozygote { two copies of the same allele

 Heterozygote { copies of two dierent alleles
Denitions

 Dominant{phenotype is seen in the heterozygote

 Recessive{phenotype is NOT seen in the heterozygote

 Incompletely dominant{heterozygote is intermediate (pink vs. red/white)

 Co-dominant{heterozygote expresses both alleles fully (AB blood type)
What makes one allele dominant over another?

 Usually recessive:
  {   Deletion or null allele
  {   Allele that makes non-functional or poorly functional product
  {   Allele that underproduces product
  {   Control mutation that disables an ON switch

 Examples:
  {   dysfunctional CF alleles
  {   temperature-sensitive color of Siamese cats
  {   O allele of ABO system
Why are nulls usually recessive?

 Most proteins produced in generous amounts

 Half of normal level generally enough

 This may buer organism against changes in internal or external
  environment
General rule for LOF mutations…
Half the amount of wild type gene product is sufficient to
give a wild type phenotype

Example : Tyrosinase                              wild type allele = C
                                                  mutant = c

[enzyme
                  threshold           wild type phenotype
activity]
                                      albino phenotype
Genotype: CC          Cc        cc



 1 wild type copy → enzyme activity above threshold needed for normal
  pigmentation, so carriers unaffected (mutant allele → recessive)
What makes one allele dominant over another?

 Usually dominant or incompletely dominant:
  {   Allele that overproduces product
  {   Control mutation that disables an OFF switch

 Examples:
  {   Adult lactase production
  {   Achondroplastic dwarsm
What makes one allele dominant over another?

 Often dominant or co-dominant:
  {   Allele that produces a novel product
  {   Control mutation that introduces a new switch

 Examples:
  {   Sickle-cell trait (disease is recessive but heterozygote has denite
      phenotype)
  {   most HLA alleles
  {   A and B alleles of ABO
Lac operon
Lac operon

 A null mutation in the inhibitor is recessive
  {   If even one copy makes usable inhibitor, LacZ is inhibited

 An inhibitor which no longer recognizes lactose is dominant
  {   The super-inhibitor will eventually turn LacZ o even if there is also
      regular inhibitor present
Lac operon

 A mutation which destroys the inhibitor binding site is dominant
  {   The uninhibited copy will produce LacZ even if the other is inhibited

 A mutation which damages LacZ is recessive
  {   The wild-type copy will continue to function
Different alleles with different outcomes… an example


                         Burmese—cbcb or cbcs or cbc


       C?


C gene codes for
tyrosinase… 1st                                                  cc
step in melanin
synthesis
                         Siamese
                       cscs or csc
What are these other alleles?
How to explain the unusual phenotypes?                  burnerkitty.com
Dierent ways to the same phenotype

 Alleles, not phenotypes, have dominance

 White color in cats can come from a dominant mutation which kills
  melanin-producing cells

 White can also come from a recessive mutation which prevents melanin
  synthesis

 One gene can have multiple eects:
  {   Dominant-mutation white cats generally deaf
  {   Recessive-mutation white cats generally normal
  {   Eye color also aected
A single mutation aecting coat and eye color




With thanks to I   Can Has Cheezburger
Codominance and incomplete dominance

 Codominant: shows the full phenotype of both alleles.

 Both alleles produce functional, but dierent, products

 Examples:
  {   A and B in the ABO blood group system
  {   HLA-DR3 and HLA-DR4

 Incompletely dominant: shows intermediate phenotype.

 Often a dosage eect

 Examples:
  {   Pink color in heterozygous 
owers
  {   Piebald color in cats
Discussion question

 Sickle cell homozygotes have severe disease due to clumping of
  hemoglobin which damages (\sickles") red blood cells

 Heterozygotes show some clumping but not severe disease

 Is this codominance or incomplete dominance?
Dominance is not superiority!

It is easy to think of dominant alleles as superior{after all, 'dominant' people
and animals tend to boss others around. However, dominance simply says
which phenotype the heterozygote has. It is not, in itself, an advantage or
disadvantage.
Examples:

 Huntington's disease{dominant is worse than recessive

 Cystic brosis{dominant is better than recessive

 Tongue rolling{probably neutral

Dominant alleles can be common or rare.
In the absence of selection, dominant alleles have no particular tendency to
increase over recessive ones.
Overdominance

Watch out! This term sounds as though it's the same kind of thing as
\dominance", but it refers to an advantage or disadvantage, not just to
which allele is expressed.

 Overdominant alleles are alleles with codominance or incomplete
  dominance in which the heterozygote is better than either homozygote.

 Sometimes called \hybrid vigor"

 Examples:
  {   Many commercially sold grains and vegetables
  {   Sickle-cell anemia
Underdominance

Again, watch out! Underdominance is not the same kind of thing as
dominance.

 Underdominant alleles are alleles with codominance or incomplete
  dominance in which the heterozygote is worse than either homozygote.

 Examples:
  {   Heterozygote of HLA-DR3 and HLA-DR4 has higher diabetes risk than
      either homozygote
  {   Mimicry in butter
ies
Underdominance

In the African butter
y Pseudacraea eurytus the orange and blue
homozygotes each resemble a local inedible species, but the heterozygote
resembles nothing in particular and is vulnerable to predators.
One-minute responses

 Tear o a half-sheet of paper

 Write one line about the lecture:
  {   Was anything unclear?
  {   Did anything work particularly well?
  {   What could be better?

 Leave at the back on your way out