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?

Distinguish between the terms mutation and mutagen, and give an example of each one.

Mutations can be harmful, neutral or beneficial. Explain what each case means and give an example of a mutation that is beneficial from the point of view of the organism carrying it.

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.

Most mutations have no consequences. Explain two reasons why many mutations go unnoticed (DNA repair systems and features of the genetic code).

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.

A child has a dominant mutation that neither of their parents has. Explain how it can appear "from scratch" (a de novo mutation) if the mutation occurred in the egg or the sperm that gave rise to that child, and whether they will be able to pass it on to their children.

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.

Tobacco, ultraviolet radiation and some viruses increase the risk of developing cancer, but not all exposed people fall ill. Explain why cancer is considered a multifactorial disease in which accumulated mutations, chance and each person's genetic predisposition play a part.

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.

To verify whether a new food additive is safe, a laboratory performs the Ames test using Salmonella bacteria unable to synthesize histidine (his⁻ strain), which cannot divide in a medium lacking this amino acid unless they experience a mutation that reverts the genetic defect.

The same number of bacteria is inoculated onto three culture plates with medium lacking histidine, and the following results are obtained after 48 hours:

• Plate 1 (control: his⁻ bacteria + distilled water): 3 colonies appear.

• Plate 2 (his⁻ bacteria + additive at low concentration, 0.1%): 4 colonies appear.

• Plate 3 (his⁻ bacteria + additive at high concentration, 5%): 395 colonies appear.

1. a) Interpret the data: why do some colonies appear on Plate 1 if there is neither histidine nor additive? What does the result of Plate 3 indicate about the effect of the additive on bacterial DNA?
2. b) Justify why a positive result in bacteria leads health agencies to reject or restrict the use of this substance in food for human consumption, explaining the biological relationship between mutagenic power and carcinogenic risk.

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.

In a population of bacteria, mutations become noticeable much faster than in a population of elephants. Relate this to their very fast asexual reproduction (a bacterium can divide every $20$ minutes) and to the huge number of individuals.

The flu virus changes slightly every year. Relate this to its high mutation rate when copying its genetic material and explain why the flu vaccine has to be updated every season while other vaccines last for years.

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.

A patient with bacterial tonsillitis stops their antibiotic treatment on the third day of the seven prescribed because they no longer have a fever or discomfort. Their reasoning is: "If I keep taking the antibiotic, the bacteria will learn to fight it and mutate to become resistant; it's better to stop now so as not to force them to mutate."

1. a) Identify the conceptual error in their reasoning and refute their statement, clearly distinguishing between the random, pre-existing nature of mutations and the selective role of the antibiotic.
2. b) Predict what will happen to the residual bacterial population in their throat if they discontinue the treatment halfway through, and reason why this misuse contributes to the proliferation of multidrug-resistant strains.

Analyze the following apparent medical and evolutionary contradiction:

1. During the Industrial Revolution, children of dark-skinned immigrant families living in foggy northern European cities suffered high rates of rickets (bone deformities due to severe deficiency in vitamin D synthesis).

2. Today, populations of British ancestry (very fair skin) living in Australia show one of the highest incidences of melanoma and blood folate degradation due to excess ultraviolet radiation.

1. a) Based on these data, refute the popular idea that "a mutation is intrinsically beneficial or harmful to a species in and of itself".
2. b) Design an evolutionary hypothesis that explains why mutations that reduced melanin synthesis were favorably selected when human groups colonized high latitudes, analyzing the biological trade-off between protection against UV radiation and vitamin D production.

In certain rural areas of sub-Saharan Africa, 25% of the adult population is heterozygous for the sickle-cell allele (genotype AS: one normal A allele and one sickle S allele), whereas homozygous sickle-cell individuals (SS) suffer from a severe disease with high mortality without hospital care.

1. a) If the S allele is lethal or very harmful in homozygosity, why hasn't natural selection eliminated it from the population? Justify your answer by comparing the biological fitness of the three possible genotypes (AA, AS, and SS) in an area with a high incidence of malaria.
2. b) If the mosquito vector transmitting malaria is completely eradicated in an isolated region through sustained biological control measures over time, predict with reasoning what will happen to the frequency of the S allele over subsequent generations.