Evolutionarily novel genes are expressed in transgenic fish tumors and their orthologs are involved in development of progressive traits in humans

Abstract

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.

Cancer, Retrogenes, and Evolution

“…Furthermore, it was noted that the expression of some evolutionarily young genes occurs specifically or preferentially in tumors. These genes were termed tumor-specifically expressed, evolutionarily novel (TSEEN) [ 38 , 98 ]. Moreover, it has been reported that new genes are also overrepresented among the testis and brain.…”

Mammalian tumor-like organs. 2. Mammalian adipose has many tumor features and obesity is a tumor-like process

“…Several non-trivial predictions of the main hypothesis have been confirmed in my laboratory ([ 1 – 4 ], reviewed in [ 5 ]). One non-trivial prediction of the main hypothesis is that evolutionarily novel organs if they indeed originated from hereditary tumors or tumor-like structures, should recapitulate some features of tumors in their development.…”

Mammalian tumor-like organs. 1. The role of tumor-like normal organs and atypical tumor organs in the evolution of development (carcino-evo-devo)

“…The prediction about the expression of evolutionarily novel genes in tumors was confirmed in many publications from our lab. As a result, a new class of genes—tumor specifically expressed, evolutionarily novel (TSEEN) genes—have been described (reviewed in [ 19 ]; see also [ 12 , 20 ]). The predicted parallel evolution of oncogenes, tumor suppressor genes, and differentiation genes was confirmed using in silico genomic analysis [ 12 ].…”

“…In the same paper, the predicted correspondence of the number of oncogenes to the number of differentiated cell types was verified [ 12 ]. The acquisition of progressive functions, not encountered in fishes, by human orthologs of fish TSEEN genes, was proven using a transgenic zebrafish inducible tumor model [ 20 ]. This paper is considered by many specialists as the direct confirmation of the main hypothesis.…”

“…This theory suggests that hereditary tumors at the earlier stages of progression might participate in the origin of new cell types, tissues, and organs through the expression of evolutionarily novel genes in tumor cells. Tumor specifically expressed, evolutionarily novel genes have been described in my lab [ 12 , 19 , 20 , 149 ].…”