title: Evolutionary origin and human-specific expansion of a cancer/testis antigen gene family.
abstract: Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution.
authors.affiliation: Department of Human Evolutionary Biology, Graduate School of Art and Science, Harvard University quzhang@post.harvard.edu sub@mail.kiz.ac.cn.
authors.forename: Qu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China quzhang@post.harvard.edu sub@mail.kiz.ac.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Su
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D005075:Biological Evolution; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D020440:Gene Duplication; D015894:Genome, Human; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D005810:Multigene Family; D010802:Phylogeny; D011323:Primates / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins
keywords: CTAGE gene family; cancer/testis antigen; gene duplication; human-specific expansion; positive selection; retroposition