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 Dawson’s beetle work shows that deleterious rare alleles may be very hard to eliminate from a gene pool because they remain hidden from selection as.

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Presentation on theme: " Dawson’s beetle work shows that deleterious rare alleles may be very hard to eliminate from a gene pool because they remain hidden from selection as."— Presentation transcript:

1  Dawson’s beetle work shows that deleterious rare alleles may be very hard to eliminate from a gene pool because they remain hidden from selection as heterozygotes.

2  This only applies if the allele is not dominant. A dominant allele is expressed both as a heterozygote and a homozygote and so is always visible to selection.

3  One way in which multiple alleles may be maintained in a population is through heterozygote advantage (also called overdominance).  Classic example is sickle cell allele.

4  Sickle cell anemia is a condition common among West Africans and those of West African descent.  Under low oxygen conditions the red blood corpuscles are sickle shaped.  Untreated the condition usually causes death in childhood.


6  About 1% of West Africans have sickle cell anemia.  A single mutation causes a valine amino acid to replace a glutamine in the alpha chain of hemoglobin  The mutation causes hemoglobin molecules to stick together.


8  Only individuals homozygous for the allele get sickle cell anemia.  Individuals with only one copy of the allele (heterozygotes) get sickle cell trait (a mild form of the disease)  Individuals with the sickle cell allele (one or two copies) don’t get malaria.



11  Heterozygotes have higher survival than either homozygote (heterozygote advantage).  Sickle cell homozygotes die of sickle cell anemia, many “normal” homozygotes die of malaria.  Stabilizing selection thus favors sickle cell allele.

12  A heterozygote advantage (or overdominance) results in a balanced polymorphism in a population.  Both alleles are maintained in the population as the heterozygote is the best combination of alleles and a purely heterozygous population is not possible.


14  Underdominance is when the heterozygote has lower fitness than either homozygote.  This situation is In this case one or other allele will go to fixation, but which depends on the starting allele frequencies


16  In some cases the costs and benefits of a trait depend on how common it is in a population.

17  In this case the commoner a phenotype is the more successful it is.  If two phenotypes are determined by single alleles one allele will go to fixation and the other be lost, but which one depends on the starting frequencies.


19  In “flat” snails individuals mate face to face and physical constraints mean only individuals whose shells coil in the same direction can mate successfully.  Higher frequencies of one coil direction leads to more mating for that phenotype and eventually it replaces the other types.


21  Under negative frequency-dependent selection a trait is increasingly favored the rarer it becomes.


23  Color polymorphism in Elderflower Orchid  Two flower colors: yellow and purple. Offer no food reward to bees. Bees alternate visits to colors.  How are two colors maintained in the population?

24  Gigord et al. hypothesis: Bees tend to visit equal numbers of each flower color so rarer color will have advantage (will get more visits from pollinators).

25  Experiment: provided five arrays of potted orchids with different frequencies of yellow orchids in each.  Monitored orchids for fruit set and removal of pollinaria (pollen bearing structures)

26  As predicted, reproductive success of yellow varied with frequency.

27 5.21 a

28  Most mutations are deleterious and natural selection acts to remove them from population.  Deleterious alleles persist, however, because mutation continually produces them.

29  When rate at which deleterious alleles being eliminated is equal to their rate of production by mutation we have mutation- selection balance.

30  Equilibrium frequency of deleterious allele q = square root of µ/s where µ is mutation rate and s is the selection coefficient (measure of strength of selection against allele; ranges from 0 to 1).  See Box 6.6 for derivation of equation.

31  Equation makes intuitive sense.  If s is small (mutation only mildly deleterious) and µ (mutation rate) is high than q (allele frequency) will also be relatively high.  If s is large and µ is low, than q will be low too.

32  Spinal muscular atrophy is a generally lethal condition caused by a mutation on chromosome 5.  Selection coefficient estimated at 0.9. Deleterious allele frequency about 0.01 in Caucasians.  Inserting above numbers into equation and solving for µ get estimated mutation rate of 0.9 X 10 -4

33  Observed mutation rate is about 1.1 X10 -4, very close agreement in estimates.  High frequency of allele accounted for by observed mutation rate.

34  Cystic fibrosis is caused by a loss of function mutation at locus on chromosome 7 that codes for CFTR protein (cell surface protein in lungs and intestines).  Major function of protein is to destroy Pseudomonas aeruginosa bacteria. Bacterium causes severe lung infections in CF patients.

35  Very strong selection against CF alleles, but CF frequency about 0.02 in Europeans.  Can mutation rate account for high frequency?

36  Assume selection coefficient (s) of 1 and q = 0.02.  Estimate mutation rate µ is 4.0 X 10 -4  But actual mutation rate is only 6.7 X 10 -7

37  Is there an alternative explanation?

38  May be heterozygote advantage.  Pier et al. (1998) hypothesized CF heterozygotes may be resistant to typhoid fever.  Typhoid fever caused by Salmonella typhi bacteria. Bacteria infiltrate gut by crossing epithelial cells.

39  Hypothesized that S. typhi bacteria may use CFTR protein to enter cells.  If so, CF-heterozygotes should be less vulnerable to S. typhi because their gut epithilial cells have fewer CFTR proteins on cell surface.

40  Experimental test.  Produced mouse cells with three different CFTR genotypes  CFTR homozygote (wild type)  CFTR/  F508 heterozygote (  F508 most common CF mutant allele)   F508/  F508 homozygote

41  Exposed cells to S. typhi bacteria.  Measured number of bacteria that entered cells.  Clear results

42 Fig 5.27a

43   F508/  F508 homozygote almost totally resistant to S. typhi.  Wild type homozygote highly vulnerable  Heterozygote contained 86% fewer bacteria than wild type.

44  Further support for idea  F508 provides resistance to typhoid provided by positive relationship between  F508 allele frequency in generation after typhoid outbreak and severity of the outbreak.

45 Fig 5.27b Data from 11 European countries

46  Another assumption of Hardy-Weinberg is that random mating takes place.  The most common form of non-random mating is inbreeding which occurs when close relatives mate with each other.

47  Most extreme form of inbreeding is self fertilization.  In a population of self fertilizing organisms all homozygotes will produce only homozygous offspring. Heterozygotes will produce offspring 50% of which will be homozygous and 50% heterozygous.  How will this affect the frequency of heterozygotes each generation?

48  In each generation the proportion of heterozygous individuals in the population will decline.


50  Because inbreeding produces an excess of homozygotes in a population, deviations from Hardy-Weinberg expectations can be used to detect such inbreeding in wild populations.

51  Sea otters once abundant along the west coast of the U.S were almost wiped out by fur hunters in the 18 th and 19 th centuries.  California population reached a low of 50 individuals (now over 1,500). As a result of this bottleneck the population has less genetic diversity than it once had.

52  Population still at a low density and Lidicker and McCollum (1997) investigated whether this resulted in inbreeding.  Determined genotypes of 33 otters for PAP locus, which has two alleles S (slow) and F (fast)

53  The genotypes of the 33 otters were: › SS 16 › SF 7 › FF 10  This gives approximate allele frequencies of S= 0.6 and F = 0.4

54  If otter population in H-W equilibrium, genotype frequencies should be › SS = 0.6* 0.6 = 0.36 › SF =2*0.6*0.4 = 0.48 › FF = 0.4*0.4 = 0.16  However actual frequencies were: › SS= 0.485, SF= 0.212, FF =0.303

55  There are more homozygotes and fewer heterozygotes than expected for a random mating population.  Having considered alternative explanations for deficit of heterozygotes Lidicker and McCollum (1997) concluded that sea otter populations show evidence of inbreedng.

56  Self-fertilization and sibling mating most extreme forms of inbreeding, but matings between more distant relatives (e.g. cousins) has same effect on frequency of homozygotes, but rate is slower.

57  F = Coefficient of inbreeding: probability that two alleles in an individual are identical by descent (both alleles are copies of a particular ancestor’s allele in some previous generation).  F increases as relatedness increases.


59  If we compare heterozygosity of inbred population H f with that of a random mating population H o relationship is  H f = H o (1-F)  Anytime F>0 frequency of heterozygotes is reduced and frequency of homozygotes naturally increases.

60  Calculating F. Need to use pedigree diagrams.  Example: Female is daughter of two half- siblings.  Two ways female could receive alleles that are identical by descent.

61 Fig 6.27a MaleFemaleMale Female Male Half-sibling mating

62 Fig 6.27b

63  Total probability of scenario is 1/16 + 1/16 = 1/8.

64  Inbreeding increases frequency of homozygotes and thus the probability that deleterious alleles are visible to selection.  In humans, children of first cousins have higher mortality rates than children of unrelated individuals.

65 Fig 6.28 Each dot on graph represents mortality rates for a human population. Mortality rate for children of cousins consistently about 4% higher than rate for children of non-relatives.

66  In a study of 2760 individuals from 25 Croatian islands Rudan et al. found a strong positive relationship between high blood pressure and the inbreeding coefficent.


68  Royal families have been particularly prone to inbreeding.  In Ancient Egypt because royal women were considered to carry the royal bloodline the pharaoh routinely was married to a sister or half-sister.

69  The most famous example of a genetic disorder exacerbated by inbreeding is the Hapsburg jaw or Hapsburg lip [severe lower jaw protrusion].  (Hapsburgs were the ruling family of Austria and Spain for much of the 1400’s- 1700’s)


71  The last of the Spanish Hapsburgs, Charles II (1661- 1700) had such severe jaw protrusion he could not chew his food properly.  Charles II also had a large number of other recessively inherited genetic problems that caused physical, mental, sexual and other problems. Charles was infertile and the last of the Spanish Hapsburg kings.



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