Abstract
BackgroundCancer/testis (CT) genes are normally expressed only in germ cells, but can be activated in the cancer state. This unusual property, together with the finding that many CT proteins elicit an antigenic response in cancer patients, has established a role for this class of genes as targets in immunotherapy regimes. Many families of CT genes have been identified in the human genome, but their biological function for the most part remains unclear. While it has been shown that some CT genes are under diversifying selection, this question has not been addressed before for the class as a whole.ResultsTo shed more light on this interesting group of genes, we exploited the generation of a draft chimpanzee (Pan troglodytes) genomic sequence to examine CT genes in an organism that is closely related to human, and generated a high-quality, manually curated set of human:chimpanzee CT gene alignments. We find that the chimpanzee genome contains homologues to most of the human CT families, and that the genes are located on the same chromosome and at a similar copy number to those in human. Comparison of putative human:chimpanzee orthologues indicates that CT genes located on chromosome X are diverging faster and are undergoing stronger diversifying selection than those on the autosomes or than a set of control genes on either chromosome X or autosomes.ConclusionGiven their high level of diversifying selection, we suggest that CT genes are primarily responsible for the observed rapid evolution of protein-coding genes on the X chromosome.
Highlights
Cancer/testis (CT) genes are normally expressed only in germ cells, but can be activated in the cancer state
We took the opportunity afforded by the publication of the initial sequence of the chimpanzee genome [18] to ask whether CT genes were conserved in man's closest evolutionary neighbour
To this end we assembled a list of human transcript sequences representing all CT gene families, and searched for homologous sequences in the human and chimpanzee genomes
Summary
Cancer/testis (CT) genes are normally expressed only in germ cells, but can be activated in the cancer state. This unusual property, together with the finding that many CT proteins elicit an antigenic response in cancer patients, has established a role for this class of genes as targets in immunotherapy regimes. MAGE genes appear to be able to mediate proliferative signals [10,11,12] and a member of the GAGE family has been shown to repress apoptosis [13], directly contributing to the malignant phenotype when aberrantly expressed in cancer. It has been suggested that a similar reprogramming may be responsible for some of the phenotype of malignant cancer cells [8,14]
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