The SPANX gene family of cancer/testis-specific antigens: rapid evolution and amplification in African great apes and hominids.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Kouprina, Natalay; Mullokandov, Michael; Rogozin, Igor B; Collins, N Keith; Solomon, Greg; Otstot, John; Risinger, John I; Koonin, Eugene V; Barrett, J Carl; Larionov, Vladimir
Year of Publication: 2004
Journal: Proc Natl Acad Sci U S A
Volume: 101
Issue: 9
Pagination: 3077-82
Date Published: 2004 Mar 2
Publication Language: eng
ISSN: 0027-8424
Keywords: Amino Acid Sequence, Animals, Antigens, Neoplasm, Chromosome Mapping, Conserved Sequence, DNA Primers, Evolution, Molecular, Exons, Gene Amplification, Gorilla gorilla, Hominidae, Humans, Macaca mulatta, Male, Molecular Sequence Data, Neoplasm Proteins, Pongo pygmaeus, Protein Isoforms, Rodentia, Saguinus, Sequence Alignment, Sequence Homology, Amino Acid, Testicular Neoplasms, Testis, X Chromosome

Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes comprise a gene family with five known members (SPANX-A1, -A2, -B, -C, and -D), encoding cancer/testis-specific antigens that are potential targets for cancer immunotherapy. These highly similar paralogous genes cluster on the X chromosome at Xq27. We isolated and sequenced primate genomic clones homologous to human SPANX. Analysis of these clones and search of the human genome sequence revealed an uncharacterized group of genes, SPANX-N, which are present in all primates as well as in mouse and rat. In humans, four SPANX-N genes comprise a series of tandem duplicates at Xq27; a fifth member of this subfamily is located at Xp11. Similarly to SPANX-A/D, human SPANX-N genes are expressed in normal testis and some melanoma cell lines; testis-specific expression of SPANX is also conserved in mouse. Analysis of the taxonomic distribution of the long and short forms of the intron indicates that SPANX-N is the ancestral form, from which the SPANX-A/D subfamily evolved in the common ancestor of the hominoid lineage. Strikingly, the coding sequences of the SPANX genes evolved much faster than the intron and the 5' untranslated region. There is a strong correlation between the rates of evolution of synonymous and nonsynonymous codon positions, both of which are accelerated 2-fold or more compared to the noncoding sequences. Thus, evolution of the SPANX family appears to have involved positive selection that affected not only the protein sequence but also the synonymous sites in the coding sequence.

DOI: 10.1073/pnas.0308532100
Alternate Journal: Proc. Natl. Acad. Sci. U.S.A.