Question

How would the mutation in Scleroporus undulatus affect melanin production?

Answer 1

In S. undulatus the replacement from histidine (wild type) to tyrosine at amino acid residue 208 is a change from a positively charged to an aromatic uncharged residue in the transmembrane region This region is important for maintaining the structural integrity of the receptor and p[lay a role in both ligand binding and signalling. As histidine remains conserved at this position in most of the vertebrates suggesting it is important for Mcr1 gene required for melanin production. Heterologous cell-based assays of signal transduction efficiency for Mc1r alleles was performed by measuring agonist-induced intracellularly cAMP levels. For S. undulatus the derived alleles exhibited reduced basal and agonist-induced cAMP formation relative to their respective wild type alleles. The 208 try allele from blanched S. undulatus showed a 24% reduction in the agonist-induced cAMP formation and a 68% decrease in basal cAMP formation compared to the wild type allele.This is associated with light coloured phenotype and this lizard evolved blanched phenotype via partial loss of function Mc1r mutations.

Mutations causing a reduction in membrane integration efficiency (as demonstrated in S. undulatus) are expected to be dominant. Because G-protein-coupled receptors (GPCRs) dimerize, if wild-type and mutant receptors are coexpressed (in a heterozygote), the mutant receptor can retain the wild-type receptor in the cellular interior and prevent its integration in the membrane.