Mutations

Explain what a mutation is and when mutations usually occur (errors in DNA copying or the action of external agents).

Distinguish between a mutation that occurs in a somatic cell (for example, a skin cell) and one that occurs in a germ cell: which of them can be passed on to offspring?

Gene mutations can be substitutions (changing one base for another), insertions (adding a base) or deletions (losing a base). Illustrate the three types by changing the word GENE and explain each one.

Reason why inserting or losing a base is usually more serious for the protein than changing one base for another, using the three-letter-word sentence "THE DOG RAN" as a model of the codon reading frame.

In a laboratory, two mutant variants of a gene encoding an essential enzyme of 320 amino acids are analyzed. In the mRNA, the normal sequence encoding amino acids 10, 11, and 12 is 5'-AUG GCU UUA-3' (methionine-alanine-leucine):

• Variant 1: undergoes a deletion of a single nucleotide (the C of the GCU codon).

• Variant 2: undergoes a deletion of the entire GCU triplet (three nucleotides are lost at once).

1. a) Knowing that in Variant 1 the new codon formed by joining the adjacent nucleotides is GUU (valine), explain what it means that the reading frame has been altered (frameshift) and how this will affect the amino acid sequence from that point to the end of the protein.
2. b) Justify which of the two variants is more likely to retain part of the functional activity of the enzyme and which will almost certainly result in a non-functional or prematurely truncated protein.

Besides the mutations that change a single base, there are chromosomal mutations that affect chunks of a chromosome or whole chromosomes. Explain the difference using the analogy of a book: changing one letter versus losing or duplicating a page.

Down syndrome is caused by the presence of three copies of chromosome 21 instead of two (trisomy 21). Explain why it is not a mutation in a specific gene but a change in the number of chromosomes, and at what point in the formation of the gametes it can arise.

Name three mutagenic agents, physical or chemical, and briefly explain how they act on DNA.

Explain the relationship between the accumulation of mutations in genes controlling the cell cycle and the development of cancer.

A patient who has had a melanoma successfully removed from their back raises two concerns during a medical appointment:

1. "I am worried that I have passed this mutation on to my newborn child."

2. "Since they have already removed my tumor and my skin is tanned and weathered, I am now immune and no longer need to use sunscreen."

Refute both statements with well-founded arguments:

1. a) Justify why their child will not inherit this melanoma, distinguishing between mutations in somatic cells and in germ cells.
2. b) Explain why it is biologically false that skin becomes "immune" to cancer, detailing the relationship between cumulative ultraviolet radiation, mutations in proto-oncogenes or tumor suppressor genes, and the loss of cell cycle control.

Mutations are said to be "the raw material for evolution". Reason why, without mutations, there would be no new genetic variation for natural selection to act upon.

Look at the diagram illustrating the genetic and cellular change in sickle cell anemia. Imagine that during genetic screening, two individuals are identified with mutations in that same codon (GAA):

• Person A: undergoes a silent point mutation where GAA changes to GAG (which also codes for glutamic acid).

• Person B: undergoes the deletion of the first base (the G is lost), altering the reading frame.

1. a) Reasonably predict the phenotype of person A at the cellular level, explaining which feature of the genetic code prevents them from developing sickle cell anemia.
2. b) Compare the expected cellular and functional impact on person B with the case of sickle cell anemia shown in the diagram. Justify why a single-nucleotide deletion is typically biologically more destructive to the protein than the point substitution shown.