Abstract

Starting from publicly-accessible datasets, we have utilized comparative and phylogenetic genome analyses to characterize the evolution of the human MAGE gene family. Our characterization of genomic structures in representative genomes of primates, rodents, carnivora, and macroscelidea indicates that both Type I and Type II MAGE genes have undergone lineage-specific evolution. The restricted expression pattern in germ cells of Type I MAGE orthologs is observed throughout evolutionary history. Unlike Type II MAGEs that have conserved promoter sequences, Type I MAGEs lack promoter conservation, suggesting that epigenetic regulation is a central mechanism for controlling their expression. Codon analysis shows that Type I but not Type II MAGE genes have been under positive selection. The combination of genomic and expression analysis suggests that Type 1 MAGE promoters and genes continue to evolve in the hominin lineage, perhaps towards functional diversification or acquiring additional specific functions, and that selection pressure at codon level is associated with expression spectrum.

Highlights

  • IntroductionThe MAGE (melanoma-associated antigen) gene family is composed of genes that all share a homologous MAGE conserved domain of approximately 200 amino acids

  • The MAGE gene family is composed of genes that all share a homologous MAGE conserved domain of approximately 200 amino acids

  • We confirmed known MAGE homologs and identified additional MAGE gene family members encoded in these genomes

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Summary

Introduction

The MAGE (melanoma-associated antigen) gene family is composed of genes that all share a homologous MAGE conserved domain of approximately 200 amino acids. In humans the family contains 37 protein-coding genes. Based on their expression patterns, MAGE genes are categorized as either Type I or II. Type II MAGEs are ubiquitously expressed in normal tissues and cancer cells. Based on their sequence relatedness, MAGE genes have been assigned to subfamilies. The Type I MAGE subfamilies MAGEA, MAGEB and MAGEC, are all located in clusters on chromosome X. Type II MAGE genes in the subfamilies MAGED, MAGEE, MAGEF, MAGEH, MAGEL and NDN are clustered on chromosome X as well as a few autosomes

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