Question

the making of the fittest: natural selection and adaptation lesson student handout a. how could the two extracellular mutations lead to the dark phenotype? (hint: think about the chemistry of the amino acids, particularly their charge.) b. how could the two intracellular mutations lead to the dark phenotype? (hint: think about the chemistry of the amino acids, particularly their charge.) c. how does the wild-type mc1r gene result in the light phenotype? (hint: it might be helpful to think of it as not resulting in the dark phenotype.)

Explanation:

(for part a as an example, same logic applies to b and c with intracellular context for b, and wild - type non - dark for c):

Part a

1. Amino Acid Charge Change: Extracellular mutations can change amino acids in the extracellular domain of the MC1R protein. For example, if a mutation changes a neutral or positively charged amino acid to a negatively charged one (or vice versa), it affects the protein's interaction with extracellular signaling molecules (like MSH or ASIP).
2. Protein - Ligand Interaction: The change in charge can alter how the protein binds to its ligands. If MC1R is a receptor, improper binding (or enhanced binding) of ligands can lead to a change in the receptor's conformation.
3. Signaling Pathway Activation: A conformational change in MC1R can trigger downstream signaling pathways (like the cAMP - dependent pathway) that regulate melanin production. If the pathway is activated more (or less, but in this case for dark phenotype, likely more), it can lead to increased production of eumelanin (the dark pigment), resulting in the dark phenotype.

Part b

1. Intracellular Amino Acid Charge: Intracellular mutations affect the amino acids in the intracellular domain of MC1R. Changing the charge of these amino acids (e.g., from non - charged to charged or between different charged states) can impact protein - protein interactions within the cell.
2. Interaction with Intracellular Molecules: These mutations can alter how MC1R interacts with intracellular signaling proteins (like G - proteins or kinases). For example, a charge change might make MC1R more likely to activate a G - protein.
3. Signaling Cascade for Melanin: Activating the intracellular signaling cascade (e.g., increasing cAMP levels or activating downstream kinases) can lead to increased melanin synthesis enzymes (like tyrosinase) activity, promoting eumelanin production and the dark phenotype.

Part c

1. Wild - Type MC1R Function: The wild - type Mc1r gene produces a MC1R protein with the correct amino acid sequence (including charge - appropriate amino acids in both extracellular and intracellular domains).
2. Ligand Binding and Signaling: It binds to its ligands (MSH or ASIP) in a regulated way. Typically, in the light phenotype, the signaling pathway for eumelanin production is not activated (or is activated at a low level). This could be because the wild - type MC1R has a lower affinity for MSH (or higher for ASIP, an inhibitor), leading to less activation of the eumelanin - producing pathway. So, instead of eumelanin, more pheomelanin (light pigment) is produced, resulting in the light phenotype.

Answer:

s (example answers for each part):

Part a

The two extracellular mutations can alter the amino acid composition of the extracellular region of the MC1R protein, changing the charge of amino acids. This charge change affects the protein's ability to bind to extracellular ligands (e.g., MSH). Altered ligand - binding can cause a conformational change in MC1R, activating downstream signaling pathways (e.g., cAMP - related) that increase eumelanin production, leading to the dark phenotype.

Part b

Intracellular mutations modify the amino acid charge in the intracellular domain of MC1R. This change impacts interactions with intracellular signaling molecules (e.g., G - proteins). Altered protein - protein interactions can activate intracellular signaling cascades (e.g., promoting cAMP production or kinase activation) that upregulate melanin - synthesis - related enzymes, increasing eumelanin production and the dark phenotype.

Part c

The wild - type Mc1r gene produces a MC1R protein with the proper amino acid sequence (including charge - correct residues in all domains). It binds to ligands (e.g., MSH, ASIP) in a way that does not strongly activate the eumelanin - producing signaling pathway. Instead, the pathway for pheomelanin (light pigment) production is favored, or eumelanin production is kept at a low level, resulting in the light phenotype.