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

BACKGROUND: Despite 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 P...

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Autores principales: Ma, Chenyu, Li, Chunyan, Ma, Huijing, Yu, Daqi, Zhang, Yufei, Zhang, Dan, Su, Tianhan, Wu, Jianmin, Wang, Xiaoyue, Zhang, Li, Chen, Chun-Long, Zhang, Yong E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724437/
https://www.ncbi.nlm.nih.gov/pubmed/36474250
http://dx.doi.org/10.1186/s13059-022-02821-9
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author Ma, Chenyu
Li, Chunyan
Ma, Huijing
Yu, Daqi
Zhang, Yufei
Zhang, Dan
Su, Tianhan
Wu, Jianmin
Wang, Xiaoyue
Zhang, Li
Chen, Chun-Long
Zhang, Yong E.
author_facet Ma, Chenyu
Li, Chunyan
Ma, Huijing
Yu, Daqi
Zhang, Yufei
Zhang, Dan
Su, Tianhan
Wu, Jianmin
Wang, Xiaoyue
Zhang, Li
Chen, Chun-Long
Zhang, Yong E.
author_sort Ma, Chenyu
collection PubMed
description BACKGROUND: Despite 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. RESULTS: By 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. CONCLUSIONS: Consistent 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02821-9.
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spelling pubmed-97244372022-12-07 Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum Ma, Chenyu Li, Chunyan Ma, Huijing Yu, Daqi Zhang, Yufei Zhang, Dan Su, Tianhan Wu, Jianmin Wang, Xiaoyue Zhang, Li Chen, Chun-Long Zhang, Yong E. Genome Biol Research BACKGROUND: Despite 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. RESULTS: By 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. CONCLUSIONS: Consistent 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02821-9. BioMed Central 2022-12-06 /pmc/articles/PMC9724437/ /pubmed/36474250 http://dx.doi.org/10.1186/s13059-022-02821-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ma, Chenyu
Li, Chunyan
Ma, Huijing
Yu, Daqi
Zhang, Yufei
Zhang, Dan
Su, Tianhan
Wu, Jianmin
Wang, Xiaoyue
Zhang, Li
Chen, Chun-Long
Zhang, Yong E.
Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
title Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
title_full Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
title_fullStr Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
title_full_unstemmed Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
title_short Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
title_sort pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724437/
https://www.ncbi.nlm.nih.gov/pubmed/36474250
http://dx.doi.org/10.1186/s13059-022-02821-9
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