D-101 Expression of evolutionarily novel genes in tumors—The possible role of tumors in evolution

Abstract

Earlier I formulated the hypothesis of the possible evolutionary role of tumors. This hypothesis suggests that heritable tumors at earlier stages of progression supply evolving multicellular organisms with extra cell masses for the expression of newly evolving genes. After expression of novel genes in tumor cells, tumors differentiate in new directions and may give rise to new cell types, tissues and organs (A.P. Kozlov, “Evolution by Tumor Neofunctionalization”, Elsevier/Academic Press, 2014). In my lab we described several genes with dual specificity—evolutionary novel genes expressed specifically or predominantly in tumors (OTP, ESRG, PVT1, ELFN1-AS1, HHLA1, DCD, SPRR1A, CLLU1, PBOV1 and others). We also described the evolutionary novelty of the whole classes of genes expressed predominantly in tumors, that is, 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 by evolutionarily novel genes. We showed the evolution of oncogenes, tumor suppressor genes and differentiation genes occurred in a parallel way, which supports the participation of tumors in the origin of new cell types. Some human genes which determine progressive traits originated in fishes and were first expressed in fish tumors. The existing data obtained in our lab and 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 conclusion will be made that the expression of evolutionarily novel genes in tumors may be a novel biological phenomenon with important evolutionary role.