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.
Earlier we suggested a new hypothesis of the possible evolutionary role of hereditary tumors (Kozlov, Evolution by tumor Neofunctionalization, 2014), and described a new class of genes – tumor specifically expressed, evolutionarily novel (TSEEN) genes - that are predicted by this hypothesis (Kozlov, Infect Agents Cancer 11:34, 2016). In this paper we studied evolutionarily novel genes expressed in fish tumors after regression, as a model of evolving organs. As evolutionarily novel genes may not yet have organismal functions, we studied the acquisition of new gene functions by comparing fish evolutionarily novel genes with their human orthologs. We found that many genes involved in development of progressive traits in humans (lung, mammary gland, placenta, ventricular septum, etc.) originated in fish and are expressed in fish tumors and tumors after regression. These findings support a possible evolutionary role of hereditary tumors, and in particular the hypothesis of evolution by tumor neofunctionalization.Research highlightsEarlier we described a new class of genes that are tumor-specifically expressed and evolutionarily novel (TSEEN). As the functions of TSEEN genes are often uncertain, we decided to study TSEEN genes of fishes so that we could trace the appearance of their new functions in higher vertebrates. We found that many human genes which are involved in development of progressive traits (placenta development, mammary gland and lung development etc.,) originated in fishes and are expressed in fish tumors.
The origin of evolutionary novel genes is connected with the origin and evolution of the novel organismal functions and the increase in morphological complexity of multicellular organisms. Novel gene acquire new or altered functions. Here we describe that evolutionary novel genes, expressed predominantly in transgenic fish tumors after their induced regression, determine progressive evolutionary characters and are conserved in human. We used a sample of genes, which were activated in inducible krasV12 transgenic zebrafish tumors according to the results of RNASeq data. Genes from our sample were expressed after HCC regression upon kras inactivation. The search of orthologs by different tools, such as blastx and psiblast, with e-value cut off not less than 10-3 and query coverage more than 50%, discovered that considerable proportion of tumor-specifically expressed genes are evolutionary novel, i.e. their orthologs are not found in Lamprey. 63 of these novel genes have orthologs in humans. Gene ontology (GO) data were used to analyze their functions. According to the results of GO some of the genes have functions not characteristic to fish. Among known functions of the human orthologues of evolutionary novel genes of zebrafish (vs. Lamprey) there are some important morphogenetic functions. For example, genes ccdc40, lmx1ba and lepa acquired functions in lung, embryonic utera and placenta, i.e. organs originated in taxa higher than fish. A large proportion of genes from our sample are connected with retina type eye, heart and brain development. Citation Format: Ekaterina Matyunina, Alexander Emelyanov, Andrei Kozlov. Evolutionary novel genes expressed in fish tumors determine progressive evolutionary characters. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1927. doi:10.1158/1538-7445.AM2015-1927
Several genes with dual specificity - evolutionarily novel and expressed specifically or predominantly in tumors (OTP, ESRG, PVT1, ELFN1-AS1, HHLA1, DCD, SPRR1A, PBOV1 and others), have been described in our lab. We suggested to call such genes Tumor Specifically Expressed, Evolutionarily Novel (TSEEN) genes. We also described the evolutionary novelty of the whole classes of genes expressed predominantly in tumors, e.g. CT-X genes and genes of noncoding tumor specifically expressed RNAs. We studied the phylogenetic distribution of the orthologs of genes expressed in tumors and found that different functional gene classes have different evolutionary novelty. Some of them are enriched with evolutionarily novel genes. We showed that phylogenetic distribution curves of oncogenes, tumor suppressor genes and differentiation genes almost coincide, i.e. their evolution proceeds in a parallel manner. Using zebrafish transgenic inducible tumor model we discovered that some human genes which determine progressive traits originated in fishes and were first expressed in fish tumors. Our data and the data published by other authors suggest that genes originated by gene duplication; from endogenous retroviruses; by exon shuffling; and de novo are expressed in tumors, sometimes with high tumor specificity. The expression of evolutionarily novel genes in tumors may be a novel biological phenomenon with important evolutionary role. Citation Format: Andrei Kozlov, Larisa Krukovskaya, Nikolai Samusik, Andrei Makashov, Ekaterina Matyunina, Julia Karnaukhova, Tamara Kurbatova, Alexander Emelyanov. Expression of evolutionarily novel genes in tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-079. doi:10.1158/1538-7445.AM2017-LB-079
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