The Attractin Gene

This week, my focus will be primarily on performing the statistical analysis of the data and conducting extensive research on the pigmentation mechanism. The statistical analysis will include the Hardy-Weinberg test to determine if the populations studied contain the expected number of alleles of each type. The Hardy Weinberg principle states that allele and genotype frequencies remain constant unless influenced by non-random mating, mutations, selection, limited population size, overlapping generations, random genetic drift (the change in the frequency in which a gene occurs in a population) and gene flow; these circumstances, however, should be present in natural populations. The extent to which the population obeys Hardy-Weinberg equilibrium will be determined with Fisher’s exact test to determine whether the expected number of heterozygotes that are present in the studied populations of rock pocket mice. Additionally, I will conduct a test to determine the extent of linkage disequilibrium (non-random association of alleles at two or more loci) among the loci expressing variation within the attractin gene and the variation in pigmentation.

With regards to the research I have been conducting, an article by H.E. Hoekstra in 2006 describes a clear description of the pigmentation production pathway. In mammals, there are two pigments: eumelanin, which creates black to brown color, and phaeomelanin, which creates red to yellow color. In melanocytes, numerous genes cause a shift between the production of these two pigments. The pigment type-switching is controlled by the interaction of the melanocortin-1 receptor (Mc1r), which encodes a seven-transmembrane receptor expressed in melanocytes, and its ligand (a molecular group that binds to another chemical entity to form a larger complex), agouti, whose protein product is secreted from dermal papilla (projections of the dermis) cells and inhibits Mc1r signaling. Without the Agouti protein, standard levels of Mc1r activity maintain levels of intracellular cyclic AMP (cAMP) to activate eumelanin synthesis. α-MSH (melanocyte-stimulating hormone) activates Mc1r and signals via cAMP. Intracellularly, the enzymes tyrosinase, tyrosinase-related protein 1 (Tyrp1), and dopachrome tautomerase (Dct), catalyze the oxidation (the removal of electrons and addition of oxygen)of tyrosine (CHNO) to dopaquinone. When all three enzymes function properly, eumelanin is deposited in melanosomes. However, in the presence of the Agouti protein, Mc1r activity is inhibited, cAMP levels are reduced, and melanocytes stop producing eumelanin and begin producing phaeomelanin. Agouti, the inverse agonist (binds to the same receptor as Mc1r but has an inverse effect) of Mc1r, binds to Mc1r with the aid of the extracellular protein Attractin (Atrn) to repress intracellular cAMP levels and switch pigment production. To produce phaeomelanin, xCT partially regulates the uptake of cystine (a white crystalline amino acid, CHNOS) (Hoekstra 2006). Thus, the interaction of the Mc1r and Agouti proteins is critical in developing pigment to be deposited in developing hairs. The full influence of surrounding genes in this pigmentation process is largely undetermined.

I am eager to continue reviewing my research that I have conducted over the past year and to determine the extent of statistical significance of the data I have obtained.