SUMMARY OF LAST TIME

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SUMMARY OF LAST TIME
SELECTION Great scope in wild populations most
individuals leave no descendents GENETIC
DRIFT Random changes in allele
frequencies inevitable in all real
populations strongest in
small populations Two special cases Bottleneck
Effect Founder
Effect
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(8) SICKLE CELL ANAEMIA
An often-told story
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HAEMOGLOBIN
4 Ironcontaining Haem groups bind oxygen
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ADULT HAEMOGLOBIN
2 alpha globins 2 beta globins
tetramer
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Beta Globin has two allelesdiffering by one
amino acid
A S
Glutamic acid Valine
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SS red blood cells
Normal shape
Sickled cell
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Alleles produce three differentgenotypes
AA AS SS Normal
Mild Severe
Anaemia Anaemia Anaemia nearly recessive
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Why does S allele do this?
S globin polymerises at low oxygen
concentrations red blood cells sickle burst
within days anaemia block capillaries

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S ALLELE IN WILD
Anthony Allison 1954
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Allele S is sometimes morethan a rare mutant
AA AS SS 9,365
2,993 29 n 12,387
Nigerian people
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Counting allele S
AA AS SS 9,365
2,993 29
2,993 58 q (2,993 58) / 2n
0.12
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HARDY-WEINBERG RATIO
p2 2pq q2

p 0.88, q 0.12
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Is population at Hardy-Weinbergratio?
p 0.88, q 0.12 AA AS
SS p2 2pq
q2 0.769 0.216 0.015
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No
For 12,387 people AA AS
SS Expected 9,524 2,675
188 Observed 9,365
2,993 29
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Far too many heterozgotesfor Hardy-Weinberg Ratio
Which assumption failed? Is there non-random
mating? Is there evolution?
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Far too many heterozgotesfor Hardy-Weinberg Ratio
Which assumption failed? Is there non-random
mating? Unlikely needs SS to tend to mate
with AA Is there evolution?
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FOUR CAUSES OF EVOLUTION

• MUTATION
• GENE FLOW
• SELECTION
• GENETIC DRIFT

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• MUTATION reject too rare

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• MUTATION reject too rare
• GENE FLOW reject too unlikely

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• MUTATION reject too rare
• GENE FLOW reject too unlikely
• GENETIC DRIFT reject population
• is large

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• MUTATION reject too rare
• GENE FLOW reject too unlikely
• GENETIC DRIFT reject population
• is large
• SELECTION heterozygote
• advantage?

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HETEROZYGOTE ADVANTAGEMAINTAINS BOTH ALLELES
AA AB BB
Relative Fitness
1 - s 1 1 - t
Allele frequencies evolve to
p t q s s t s t
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S allele also affectsresistance to
malariaRESISTANT?
AA AS SS No
Yes Yes Resistance
dominant
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Why does S allele do this?
Malaria parasites

• take longer to enter sickled cells
• - when they do, cause oxygen crash

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So what happens to allele S when it arrives in
population?
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HARDY-WEINBERG RATIO
p2 2pq q2

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RARE ALLELES ARE MAINLY IN HETEROZYGOTES
Proportion of alleles in heterozygote bodies
frequency of allele
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New rare allele S
Almost always in heterozygotes AS if no
malaria occurs, slight anaemia
SELECTED AGAINST if
malaria occurs, resistance makes it
fitter SELECTED FOR
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EXPECT S TO BE COMMONER IN MALARIAL AREAS
Malaria
S allele
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RELATIVE FITNESSES SELECTION COEFFICIENTS
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Can predict allele frequencyfor heterozygote
advantage
Predicted q s / (s t) 0.11
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Can predict allele frequencyfor heterozygote
advantage
Predicted q s / (s t) 0.11 Observed q
0.12 from other data Consistent with hypothesis
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ALLELE K
A rarely told tale of sickle cell
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There is a third allele K so three extra
genotypes
AK SK KK
Anaemia
Very high
resistance K
resistance is recessive
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Why does K allele do this?

• K globin does not polymerise at low oxygen
  concentration cannot cause anaemia
• Haemoglobin damaged by parasites drop haem groups
  releasing oxygen cell parasites die

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KK is the best genotyperelative fitness, AS
1
worse than AS
same as AA
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but what happens to allele K when it arrives in
population?
KK is the best genotype
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HARDY-WEINBERG RATIO
p2 2pq q2

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RARE ALLELES ARE MAINLY IN HETEROZYGOTES
Proportion of alleles in heterozygote bodies
frequency of allele
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New rare allele K
Almost always in heterozygotes AK no
advantage, same fitness as AA SK selected
against, worse than AS
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Allele K cannot spread byselection But a few
human populationsare fixed for KHOW?
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EXAMPLE KWELA
Mozambique