# Exercise 5.1

## Natural Selection and the Preservation of Genetic Diversity

### INTRODUCTION

Although the action of natural selection often results in a reduction of genetic diversity, some forms of selection (collectively known as balancing selection) can maintain genetic diversity. One form of balancing selection is heterozygote advantage, where the heterozygote has a higher fitness than either homozygote. Heterozygote advantage is sometimes called overdominance for fitness.

Perhaps the best-known case of heterozygote advantage is sickle cell anemia in humans. Homozygotes for the sickle cell allele usually die before child-bearing years, particularly in less-developed areas of the world. Despite the low fitness of the homozygotes, the allele for sickle cell anemia can persist in malaria-infested regions of the world because heterozygotes have increased resistance to malaria. Other likely examples of heterozygote advantage include cystic fibrosis in humans, alleles at the Human Leukocyte Antigen (HLA) system in humans, and resistance to the pesticide warfarin in rats.

In this exercise, you will perform simulations that show the power of heterozygotye advantage.

### QUESTIONS

Set the population size to 100, with 25 AA, 50 Aa, and 25 aa individuals.

Question 1. What is the initial frequency of the A allele?

Question 2. Is the population at Hardy–Weinberg equilibrium (see textbook Chapter 4, pp. 83–85)?

Question 3. If the initial frequency of the A allele were 0.3 and the population size were 100, how many individuals of each genotype would be in the population at Hardy–Weinberg equilibrium?

Set the fitnesses of all three genotypes (AA, Aa, aa) to 1.0. All genotypes thus have equal fitnesses.

Run the simulation. Record if the A allele is fixed, lost, or remains polymorphic throughout the 400 generations. If the A allele remains polymorphic, record whether its frequency stayed between 0.25 and 0.75 (see lines on chart of frequency). Repeat for a total of 20 trials.

Question 4. In how many trials did the A allele fix? In how many trials was it lost? In how many was it polymorphic? In the cases where the A allele remains polymorphic after 400 generations, in how many trials did its frequency remain between 0.25 and 0.75 throughout the 400 generations?

Question 5. What evolutionary processes caused the changes in frequency of the A allele? What evolutionary processes caused the loss and fixation of the A allele in those cases where it was lost or fixed?

Set the fitnesses of the genotypes so that the fitness of AA is 0.8, the fitness of Aa is 1.0, and the fitness of aa is 0.8. This is a case of heterozygote advantage.

Run the simulation. Record if the A allele is fixed, lost, or remains polymorphic throughout the 400 generations. If the A allele remains polymorphic, record whether its frequency stayed between 0.25 and 0.75 (see lines on chart of frequency). Repeat for a total of 10 trials.

Question 6. In how many trials did the A allele fix? In how many trials was it lost? In how many was it polymorphic? In the cases where the A allele remains polymorphic after 400 generations, in how many trials, did its frequency remain between 0.25 and 0.75 throughout the 400 generations?

Question 7. What evolutionary process is counteracted by balancing selection by heterozygote advantage in the last simulations you performed?

Set the initial frequency of the A allele to 0.8 by starting the population with 128 AA, 64 Aa, and 8 aa individuals. Maintain the same values for fitness: fitness of AA is 0.8, the fitness of Aa is 1.0, and the fitness of aa is 0.8. Run the simulation three times.

Question 8. Describe what happens to the frequency of the A allele.