EVOLUTION OF THE PRIMATE ANDROGEN RECEPTOR - A STRUCTURAL BASIS FOR DISEASE

Androgen effects mediated by the androgen receptor (AR) are essential for male reproductive development and virilization. Comparison of AR D NA coding sequence from five primate species, Homo sapiens (human), Pa n troglodytes (chimpanzee), Papio hamadryas (baboon), Macaca fascicula ris (macaque), and Eulemur fulvus collaris (collared brown lemur), sup ports their phylogeny with complete conservation of the DNA and steroi d binding domain protein sequence. A linear increase in trinucleotide repeat expansion of homologous CAG and GGC sequences occurs in the NH2 -terminal transcriptional activation region and is proportional to the time of species divergence. A serine phosphate/glutamine repeat inter action is observed where increasing CAG repeat length is associated wi th an increased rate of serine 94 phosphorylation. Disparity in the ca lculated and apparent molecular weight with CAG repeat expansion of an AR NH2-terminal fragment suggests self-aggregation with increasing gl utamine repeat length into the pathological range. These results sugge st that a CAG/glutamine repeat expanded during divergence of the highe r primate species, which may have a direct effect on AR structure and support a common pathway in CAG trigenic diseases in the pathophysiolo gy of neurodegeneration observed in X-linked spinal bulbar and muscula r atrophy.