Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum

Genome Biology

Research

Li Zhang¹  Chun-Long Chen²  Jianmin Wu³  Huijing Ma⁴  Dan Zhang⁴  Tianhan Su⁵  Chenyu Ma⁵  Daqi Yu⁵  Yong E. Zhang⁶  Yufei Zhang⁷  Chunyan Li⁸  Xiaoyue Wang⁹ 

[1] Chinese Institute for Brain Research, 102206, Beijing, China;Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3244, Dynamics of Genetic Information, 75005, Paris, France;Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center for Cancer Bioinformatics, Peking University Cancer Hospital & Institute, 100142, Beijing, China;Key Laboratory of Zoological Systematics and Evolution & State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China;Key Laboratory of Zoological Systematics and Evolution & State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China;University of Chinese Academy of Sciences, 100049, Beijing, China;Key Laboratory of Zoological Systematics and Evolution & State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China;University of Chinese Academy of Sciences, 100049, Beijing, China;Chinese Institute for Brain Research, 102206, Beijing, China;CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223, Kunming, China;Key Laboratory of Zoological Systematics and Evolution & State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China;University of Chinese Academy of Sciences, 100049, Beijing, China;School of Life Sciences, Nanjing University, 210093, Nanjing, China;School of Engineering Medicine, Key Laboratory of Big Data-Based Precision Medicine (Ministry of Industry and Information Technology), and Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 100191, Beijing, China;State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China;

关键词: Molecular atavism;    Antagonistic pleiotropy;    Primate-specific genes;    Cancer evolution;    Brain evolution;    Cell cycle;    Gene duplication;    DDX11;   

DOI  :  10.1186/s13059-022-02821-9

 received in 2021-09-27, accepted in 2022-11-24,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundDespite having been extensively studied, it remains largely unclear why humans bear a particularly high risk of cancer. The antagonistic pleiotropy hypothesis predicts that primate-specific genes (PSGs) tend to promote tumorigenesis, while the molecular atavism hypothesis predicts that PSGs involved in tumors may represent recently derived duplicates of unicellular genes. However, these predictions have not been tested.ResultsBy taking advantage of pan-cancer genomic data, we find the upregulation of PSGs across 13 cancer types, which is facilitated by copy-number gain and promoter hypomethylation. Meta-analyses indicate that upregulated PSGs (uPSGs) tend to promote tumorigenesis and to play cell cycle-related roles. The cell cycle-related uPSGs predominantly represent derived duplicates of unicellular genes. We prioritize 15 uPSGs and perform an in-depth analysis of one unicellular gene-derived duplicate involved in the cell cycle, DDX11. Genome-wide screening data and knockdown experiments demonstrate that DDX11 is broadly essential across cancer cell lines. Importantly, non-neutral amino acid substitution patterns and increased expression indicate that DDX11 has been under positive selection. Finally, we find that cell cycle-related uPSGs are also preferentially upregulated in the highly proliferative embryonic cerebrum.ConclusionsConsistent with the predictions of the atavism and antagonistic pleiotropy hypotheses, primate-specific genes, especially those PSGs derived from cell cycle-related genes that emerged in unicellular ancestors, contribute to the early proliferation of the human cerebrum at the cost of hitchhiking by similarly highly proliferative cancer cells.

【 授权许可】

CC BY   
© The Author(s) 2022

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