Evolution of Melanoma Antigen-A11 (<italic>MAGEA11</italic>) During Primate Phylogeny.

Melanoma antigen-A11 (MAGE-A11) is an X-linked and primate-specific steroid hormone receptor transcriptional coregulator and proto-oncogenic protein whose increased expression promotes the growth of prostate cancer. The <italic>MAGEA11</italic> gene is expressed at low levels in normal human testis, ovary, and endometrium, and at highest levels in castration-resistant prostate cancer. Annotated genome predictions throughout the surviving primate lineage show that <italic>MAGEA11</italic> acquired three 5′ coding exons unique within the <italic>MAGEA</italic> subfamily during the evolution of New World monkeys (NWM), Old World monkeys (OWM), and apes. MAGE-A11 in all primates has a conserved F<italic>XX</italic>IF coactivator-binding motif that suggests interaction with p160 coactivators contributed to its early evolution as a transcriptional coregulator. An ancestral form of MAGE-A11 in the more distantly related lemur has significant amino acid sequence identity with human MAGE-A11, but lacks coregulator activity based on the absence of the three 5′ coding exons that include a nuclear localization signal (NLS). NWM MAGE-A11 has greater amino acid sequence identity than lemur to human MAGE-A11, but inframe premature stop codons suggest that <italic>MAGEA11</italic> is a pseudogene in NWM. MAGE-A11 in OWM and apes has nearly identical 5′ coding exon amino acid sequence and conserved interaction sites for p300 acetyltransferase and cyclin A. We conclude that the evolution of <italic>MAGEA11</italic> within the lineage leading to OWM and apes resulted in steroid hormone receptor transcriptional coregulator activity through the acquisition of three 5′ coding exons that include a NLS sequence and nonsynonymous substitutions required to interact with cell cycle regulatory proteins and transcription factors. [ABSTRACT FROM AUTHOR]