In order to be inherited in progeny generations, novel genes should originate in germ cells. Here, we suggest that the testes may play a special “catalyst” role in the birth and evolution of new genes. Cancer/testis antigen encoding genes (CT genes) are predominantly expressed both in testes and in a variety of tumors. By the criteria of evolutionary novelty, the CT genes are, indeed, novel genes. We performed homology searches for sequences similar to human CT in various animals and established that most of the CT genes are either found in humans only or are relatively recent in their origin. A majority of all human CT genes originated during or after the origin of Eutheria. These results suggest relatively recent origin of human CT genes and align with the hypothesis of the special role of the testes in the evolution of the gene families. 1. Introduction In order to be inherited in progeny generations, novel genes should originate in germ cells. Available data suggest that the generation of novel genes in germ cells is ongoing process, for example, the promiscuity of gene expression in spermatogenic cells [1, 2]. Novel genes may originate through different mechanisms (retrogenes, segmental duplicates, chimeric, and de novo emerged genes), but all of them are uniformly expressed in the testis ([3–8]; reviewed in [9]). These observations led us to suggest that testes may play a “tissue catalyst” role in the birth and evolution of new genes [9]. Previously, we proposed the expression of evolutionarily novel genes in tumors [10]. Cancer/testis or cancer/germline antigen genes are a class of genes with predominant expression in testis and in a variety of tumors, with a significant exclusion of some CT antigens also expressed in the brain. Here we set forth to test the hypothesis that cancer/testis antigen genes should be composed of evolutionarily new or young gene family. We performed homology searches for sequences similar to human CT in various animals. Additionally, as an extensive traffic of novel genes has been described for mammalian X chromosome [3, 6, 11], we also performed this analysis separately for genes located on this chromosome only. 2. Methods The list of CT antigens gene was retrieved from CT Database (http://www.cta.lncc.br) and included 265 genes. Among them, there are 105 CT antigens that are encoded by the X chromosome (CT-X genes) and 105 that are located on various autosomes (autosome CT genes, or non-X CT genes). Eight CT antigen encoding genes are located on the Y chromosome. To assess the evolutionary novelty of the studied group
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