In mammals, the dark color of skin, hair, and eyes is due to a pigment called melanin. Melanin is produced by specialized skin cells called melanocytes. The melanin is then transferred to other skin cells called keratinocytes. Melanocytes synthesize melanin in a multistep metabolic pathway (Figure 1). The amount of melanin produced is dependent on the amount of the enzymes TYR, TRP2, and TRP1 present inside melanocytes.
The figure presents 5 steps in the melanin synthesis pathway. The enzyme T Y R catalyzes the conversion of tyrosine to L D O P A and then the conversion of L D O P A to D O P A quinone. D O P A is then converted to D O P A chrome. T R P 2 catalyzes the conversion of D O P A chrome to D H I C A, and the enzyme T R P 1 catalyzes the conversion of D H I C A to Melanin.
Figure 1. Melanin synthesis pathway
The peptide hormone α–melanocyte stimulating hormone (α–MSH) activates a signal transduction pathway leading to the activation of MITF. MITF is a transcription factor that increases the expression of the TYR, TRP2, and TRP1 genes (Figure 2).
The figure presents multiple steps in the signal transduction pathway leading to activation of melanin synthesis genes in melanocytes. The hormone alpha M S H binds to the M C 1 R protein in the cell membrane. This activates a G protein that also has G T P bound to it. The G protein binds to and activates adenylyl cylase in the cell membrane. Adenyl cyclase catalyzes the conversion of A T P to c A M P. This leads to activation of Protein Kinase A, which then activates C R E B, which then activates M I T F. M I T F increases the expression of T Y R, T R P 2, and T R P 1 in the nucleus.
Figure 2. Activation of melanin synthesis genes in melanocytes
Some mammals increase melanin production in response to ultraviolet (UV) radiation. The UV radiation causes damage to DNA in keratinocytes, which activates the p53 protein. p53 increases the expression of the POMC gene. The POMC protein is then cleaved to produce α–MSH. The keratinocytes secrete α–MSH, which signals nearby melanocytes. The increased melanin absorbs UV radiation, reducing further DNA damage.
The figure presents a model of production of alpha M S H in keratinocytes in response to U V radiation. The UV radiation causes D N A damage. The damage activates the p 53 protein, which in turn increases the expression of the P O M C gene. Ribosomes translate the P O M C m R N A. The protein produced is cleaved, producing alpha M S H.
Figure 3. Production of α–MSH in keratinocytes in response to UV radiation
Researchers discovered a mutant form of the TYR gene with a deletion of a single guanine nucleotide in the beginning of the coding sequence.
Which of the following best predicts the phenotype of an individual who is homozygous for this TYR mutation?
The mutation will cause a single amino acid change in the TYR protein, which will not be enough to disrupt its function. Therefore, those with this mutation will produce melanin in the hair, skin, and eyes and tan in response to UV radiation.
A
The mutation will cause a single amino acid change in the TYR protein, leading to a nonfunctional TYR protein. Therefore, those with this mutation will lack melanin in the hair, skin, and eyes and will not tan in response to UV radiation.
B
The mutation will change all subsequent amino acids in the TYR protein, leading to nonfunctional TYR protein. Since the TRP1 and TRP2 genes were not affected, the TRP1 and TRP2 proteins will fill the role of the TYR protein. Therefore, those with this mutation will produce melanin in the hair, skin, and eyes in response to UV radiation.
C
The mutation will change all subsequent amino acids in the TYR protein, leading to nonfunctional TYR protein. Individuals with this mutation will lack melanin in their hair, skin, and eyes and will not tan in response to UV radiation.
D
