Oncogenes, tumor suppressor and differentiation genes represent the oldest human gene classes and evolve concurrently

Makashov, A. A.; Malov, Sergey V.; Kozlov, А. P.

doi:10.1038/s41598-019-52835-w

Cited by 22 publications

(38 citation statements)

References 53 publications

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“…2017 ). Oncogenes and tumor suppressor genes were found to be among the evolutionarily oldest sets of genes in eukaryotes, associated with the timing of the origins of both multicellular and vertebrate life ( Makashov et al. 2019 ); this is consistent with our observation that oncogenes are highly conserved at the sequence level.…”

Section: Discussionsupporting

confidence: 91%

The Evolution of Human Cancer Gene Duplications across Mammals

Tollis

Schneider-Utaka

Maley

2020

Molecular Biology and Evolution

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Cancer is caused by genetic alterations that affect cellular fitness, and multicellular organisms have evolved mechanisms to suppress cancer such as cell cycle checkpoints and apoptosis. These pathways may be enhanced by the addition of tumor suppressor gene paralogs or deletion of oncogenes. To provide insights to the evolution of cancer suppression across the mammalian radiation, we estimated copy numbers for 548 human tumor suppressor gene and oncogene homologs in 63 mammalian genome assemblies. The naked mole rat contained the most cancer gene copies, consistent with the extremely low rates of cancer found in this species. We found a positive correlation between a species’ cancer gene copy number and it’s longevity, but not body size, contrary to predictions from Peto’s Paradox. Extremely long-lived mammals also contained more copies of caretaker genes in their genomes, suggesting that the maintenance of genome integrity is an essential form of cancer prevention in long-lived species. We found the strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes, suggesting selection has acted to suppress both hereditary and sporadic cancers. We also found a strong relationship between the number of tumor suppressor genes and the number of oncogenes in mammalian genomes, suggesting complex regulatory networks mediate the balance between cell proliferation and checks on tumor progression. This study is the first to investigate cancer gene expansions across the mammalian radiation and provides a springboard for potential human therapies based on evolutionary medicine.

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Section: Discussionsupporting

confidence: 91%

The Evolution of Human Cancer Gene Duplications across Mammals

Tollis

Schneider-Utaka

Maley

2020

Molecular Biology and Evolution

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“…After the origin of a new cell type, the corresponding oncogene should have turned into a cell type-specific regulator of cell division and gene expression [26,27]. Non-trivial predictions that follow from such a scenario were confirmed in my lab and discussed in the previous paper [3].…”

Section: Tumors and The Origin Of New Cell Typesmentioning

confidence: 95%

The Role of Heritable Tumors in Evolution of Development: a New Theory of Carcino-evo-devo

Kozlov

2019

Acta Naturae

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The hypothesis of evolution by tumor neofunctionalization (the main hypothesis) describes the possible role of hereditary tumors in evolution. The present article examines the relationship of the main hypothesis to other biological theories. As shown in this paper, the main hypothesis does not contradict to the existing biological theories, but fills the lacunas between them and explains some unexplained (or not completely understood) questions. Common features of embryonic development and tumorigenesis are described by several recognized theories. Similarities between normal development and tumorigenesis suggest that tumors could participate in the evolution of ontogenesis and in the origin of new cell types, tissues and organs. A wide spectrum of non-trivial explanations and non-trivial predictions in different fields of biology, suggested by the main hypothesis, is an indication of its fundamental nature and the potential to become a new biological theory, a theory of the role of tumors in evolution of development, or carcino-evo-devo.

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“…Tumors are widespread and are represented throughout the phylogenetic tree (reviewed in [ 2 , 10 , 11 ]). Proto-oncogenes and tumor suppressor genes are the oldest gene classes [ 12 ]. Tumors and cancer-related genes originated during the early period of evolution of multicellular organisms [ 2 , 13 , 14 ].…”

Section: Background: the Theory Of Carcino-evo-devomentioning

confidence: 99%

“…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 ].…”

Section: Background: the Theory Of Carcino-evo-devomentioning

confidence: 99%

“…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 ].…”

Section: Background: the Theory Of Carcino-evo-devomentioning

confidence: 99%

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

Kozlov

2022

Infect Agents Cancer

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Background Earlier I hypothesized that hereditary tumors might participate in the evolution of multicellular organisms. I formulated the hypothesis of evolution by tumor neofunctionalization, which suggested that the evolutionary role of hereditary tumors might consist in supplying evolving multicellular organisms with extra cell masses for the expression of evolutionarily novel genes and the origin of new cell types, tissues, and organs. A new theory—the carcino-evo-devo theory—has been developed based on this hypothesis. Main text My lab has confirmed several non-trivial predictions of this theory. Another non-trivial prediction is that evolutionarily new organs if they originated from hereditary tumors or tumor-like structures, should recapitulate some tumor features in their development. This paper reviews the tumor-like features of evolutionarily novel organs. It turns out that evolutionarily new organs such as the eutherian placenta, mammary gland, prostate, the infantile human brain, and hoods of goldfishes indeed have many features of tumors. I suggested calling normal organs, which have many tumor features, the tumor-like organs. Conclusion Tumor-like organs might originate from hereditary atypical tumor organs and represent the part of carcino-evo-devo relationships, i.e., coevolution of normal and neoplastic development. During subsequent evolution, tumor-like organs may lose the features of tumors and the high incidence of cancer and become normal organs without (or with almost no) tumor features.

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Oncogenes, tumor suppressor and differentiation genes represent the oldest human gene classes and evolve concurrently

Cited by 22 publications

References 53 publications

The Evolution of Human Cancer Gene Duplications across Mammals

The Evolution of Human Cancer Gene Duplications across Mammals

The Role of Heritable Tumors in Evolution of Development: a New Theory of Carcino-evo-devo

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

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