The correlation shown in the data above can be explained by natural selection. Outline how the process of natural selection can lead to evolution.

Explain how a base substitution mutation, such as GAG to GTG, can lead to a disease like sickle-cell anemia.

Using a Punnett grid, determine the possible genotypes and phenotypes of a cross between a man and a woman who are both carriers of the sickle-cell allele. Use the symbol Hb^S for the sickle-cell allele and Hb^A for the normal allele.

Phenotypes:
 

offspring compete/environment cannot support all offspring;
(genetic) variation in the offspring;
natural selection /survival of better adapted/fittest organisms;
reproduction passes characteristics to other generations;
allele frequencies change;
malaria causes selection pressure (in Africa/worldwide);
different hemoglobin/sickle-cell genotypes exist / normal hemoglobin and sicklecell alleles exist;
natural selection/resistance to malaria of sickle-cell heterozygotes/allele;
survivors pass on sickle-cell allele to offspring; (do not accept sickle-cell anemia)
frequency of sickle-cell allele highest in areas of high malaria incidence;

change in the codon (of the mRNA);
tRNA with a different anticodon attaches;
(if codon changed) wrong/different amino acid is joined to peptide/glutamic acid replaced by valine;
distorted hemoglobin molecule alters red blood cell shape/reduces ability to carry oxygen;

(genotypes shown in a Punnett grid eg)

(phenotypes)
(Hb^A Hb^A) normal and (Hb^A Hb^S) normal carrier/intermediate/sickle-cell trait and (Hb^S Hb^S) sickle-cell anemia/diseased / (Hb^A Hb^A and Hb^A Hb^S) normal /symptomless and (Hb^S Hb^S) sickle-cell anemia/diseased;
To award the mark all phenotypes must be mentioned.

Much stimulus material is given about malaria and sickle-cell anemia in the stem for 4(a), yet the final question can be answered without any reference to the stem. This may have caused uncertainty among candidates. An effort was made to accommodate general answers about natural selection leading to evolution as well as those that included the malaria information given in the stem. Some candidates inaccurately used the term “sickle-cell anemia” when they should have written “sickle-cell allele.”  

Few candidates recognized that a base substitution mutation causes the structural defect in hemoglobin which causes sickle-cell anemia for 4(b). Hemoglobin was rarely mentioned. A change in the codon of mRNA and the consequent attachment of a tRNA with a different anticodon and amino acid was just not given. There was almost no reference to codon or anticodon. Candidates proffered less detailed answers such as “a different amino acid is joined to the peptide” or “glutamic acid is replaced by valine”.

A few candidates confused sickle-cell anemia and Hb inheritance with sex-linkage in 4(c), perhaps because of wording in the stem. Some listed genotypes instead of describing phenotypes for the second part of the answer. All phenotypes had to be given for the mark. Since the guide (4.3.12) regards Hb^A and Hb^S as codominant alleles, describing or stating the phenotype of the carrier is problematic since carrier status “appears” the same as homozygous normal. This problem was covered by the mark scheme as each of the following was accepted to describe the carrier phenotype: normal, normal carrier, intermediate, sickle-cell trait and symptomless. Regardless of how the carrier phenotype was described the phenotype of sickle-cell anemia/diseased had to be mentioned. Those who drew a correct Punnett grid usually did well in describing the phenotypes.