Chemistry of Heredity

This is a dry lab whose goal is to have students discover the consequences of two different kinds of mutations, base substitution and frameshift (insertion or deletion), while giving them the chance to practice using the genetic code to deduce amino acid sequences coded in four DNA sequences. We deliberately devised the DNA sequences to emphasize the general unpredictability of the results of base substitutions due to the code's degeneracy.

The four DNA sequences we give them are as follows:

1. T-A-C-G-C-T-T-T-G-A-T-A-T-C-G-C-C-T
2. T-A-C-G-C-C-T-T-A-A-T-G-A-G-G-C-C-C
3. T-A-C-A-G-C-T-T-T-G-A-T-A-T-C-G-C-C
4. T-A-C-T-G-C-C-T-T-A-A-T-G-A-G-G-C-C

They are to deduce the RNA sequence resulting from transcription and the amino acid sequence resulting from translation. Then they are told that DNAs 2, 3, and 4 arose by various mutations from DNA 1. They are asked (1) to describe the mutations responsible for changing DNA 1 to DNA 2, DNA 1 to DNA 3, and DNA 2 to DNA 4, (2) to explain why there was no change in the amino acid sequence even after six base substitutions, and (3) why the single base difference between DNA 1 and 3 had such a big effect. Another question asks them to contrast the statistical frequencies of stop codons among codons (1) in the genetic code table and (2) among in-frame codons in real coding sequences and the reason for the appearance of a rare stop codon from DNA 3. Finally, they are told that the sixth codon in human hemoglobin-beta RNA is GAG and asked (1) what is the DNA sequence giving rise to that codon, (2) what is the sixth amino acid in hemoglobin-beta, and (3) what mutation must have happened in the DNA to give rise to valine in this position in sickle-cell anemia.

An important detail that I skip over in this course is the difference between 3' and 5' ends in DNA and RNA. Some students struggle hard enough with concepts of bases, DNA vs. RNA, and transcription and translation that I didn't want to risk losing some with an intrinsically unnecessary item.

Revised 9/1/06