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

A A Makashov,S V Malov,A P Kozlov

doi:10.1038/s41598-019-52835-w

Abstract

Earlier we showed that human genome contains many evolutionarily young or novel genes with tumor-specific or tumor-predominant expression. We suggest calling such genes Tumor Specifically Expressed, Evolutionarily New (TSEEN) genes. In this paper we performed a study of the evolutionary ages of different classes of human genes, using homology searches in genomes of different taxa in human lineage. We discovered that different classes of human genes have different evolutionary ages and confirmed the existence of TSEEN gene classes. On the other hand, we found that oncogenes, tumor-suppressor genes and differentiation genes are among the oldest gene classes in humans and their evolution occurs concurrently. These findings confirm non-trivial predictions made by our hypothesis of the possible evolutionary role of hereditary tumors. The results may be important for better understanding of tumor biology. TSEEN genes may become the best tumor markers.

Highlights

Earlier we showed that human genome contains many evolutionarily young or novel genes with tumorspecific or tumor-predominant expression
Hereditary tumors were the source of extra cell masses which could be used in the evolution of multicellular organisms for the expression of evolutionarily novel genes, for the origin of new differentiated cell types with novel functions and for building new structures which constitute evolutionary innovations and morphological novelties
The median ages of other groups of genes are the following: oncogenes (750 million years (Ma)), tumor suppressor genes (750 Ma), differentiation genes (693 Ma), homeobox genes (450 Ma), apoptosis genes (360 Ma), canser/testis (CT) antigen genes (324 Ma), Biomedical Center globally subtracted, tumor- expressed (BMC GSTSE) protein-coding genes (220 Ma), BMC GSTSE non-coding sequences (130 Ma), CT antigen genes located on X chromosome (CT-X) (60 Ma) and BMC GSTSE non-coding sequences located on X chromosome (BMC GSTSE-X non-coding sequences) (50 Ma) (Fig. 2)

Summary

Introduction

Earlier we showed that human genome contains many evolutionarily young or novel genes with tumorspecific or tumor-predominant expression. We found that oncogenes, tumorsuppressor genes and differentiation genes are among the oldest gene classes in humans and their evolution occurs concurrently These findings confirm non-trivial predictions made by our hypothesis of the possible evolutionary role of hereditary tumors. In previous publications[1,2,3,4,5] we formulated the hypothesis of the possible evolutionary role of hereditary tumors, i.e. tumors that can be passed from parent to offspring According to this hypothesis, hereditary tumors were the source of extra cell masses which could be used in the evolution of multicellular organisms for the expression of evolutionarily novel genes, for the origin of new differentiated cell types with novel functions and for building new structures which constitute evolutionary innovations and morphological novelties. We performed a systematic study of the evolutionary ages of different functional classes of human genes in order to verify one more nontrivial prediction of the hypothesis of the possible evolutionary

Methods

Results

Conclusion