Malaria, Anemia, and the \"Sickle Cell\" phenotype -- The True Story The story y

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Malaria, Anemia, and the "Sickle Cell" phenotype -- The True Story

The story you learned in high school biology or 1st-year college biology concerning a balanced polymorphism of A ("normal") and S ("sickle cell") in malaria regions of Africa is incomplete. There are actually 3 alleles at the "sickle cell" locus (Let's call the third allele "C"), rather than the two alleles we usually learn. So there are 6 genotypes instead of 3, and the AS genotype is not the most fit in the presence of malaria Where malaria is prevalent, the CC genotype is substantially more fit than any other (see table below).

Genotype Fitness Condition

AA (A3A3) 0.64 Malarial susceptibility

AS (A3A2) 0.77 Malarial resistance

SS (A2A2) 0.15 Anemia

AC (A3A1) 0.64 Malarial susceptibility

SC (A2A1) 0.54 Anemia

CC (A1A1) 1.00 Malarial resistance

The AA genotype is the most fit where there is no malarial, so the “C” and “S” alleles are were at very low frequencies (around 10-5) maintained by mutation in the non-malarial parts of Africa where humans lived at first. When humans later migrated into malarial parts of Africa from non-malarial regions, the migrant population had the allele frequencies of non-malarial regions: the normal allele "A" was nearly fixed, while alleles "S" (the sickle cell allele) and "C" were at very low frequencies. Over time, the blood genotype frequencies of the migrant populations evolved to achieve a higher average fitness.

However, these populations did NOT achieve the highest possible average fitness. Today, the A and S alleles are present in high frequencies maintained by the heterozygote superiority, and C is maintained by mutation at a very low frequency.

Based on this given information, the following two questions are the ones I need help answering.
8.Using the information in the table of genotype fitnesses in a malarial region (on page 6 of this hand-out), compute the average fitness of a population with fixation of allele “C” (1 pt), and the average fitness of a population with allele “A” and allele “S” in a balanced polymorphism (3 pts).

8B. Explain why the C allele has not been fixed in human populations in malarial regions of Africa, even though the CC genotype has the highest fitness of all possible genotypes (4 pts). Hint: think of rates of allelic substitution when allele frequencies are very low in heterozygote advantage and especially heterozygote disadvantage.

Explanation / Answer

8)

The average fitness of the population with the fixation of allele C is fitness of CC genotype/the highest fitness.

So, 1/1 = 1

The average fitness of the population with allele A and S is 0.77/1 = 0.77.

8B)

C allele alone may not be sufficient for its survival and fitness in the population. It had to depend on the alleles A and S. Though the allele frequencies are low for A and S as heterozygotes, when they are combined with C, their fitness levels will change.

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