Bioinformatic prediction of critical genes and pathways involved in longevity in Drosophila melanogaster

Li, Jia-qi; Duan, Dan-dan; Zhang, Jian-qin; Zhou, Yu-zhi; Qin, Xue-mei; Du, Guan-hua; Gao, Li

doi:10.1007/s00438-019-01589-1

Original Article
Published: 20 July 2019

Bioinformatic prediction of critical genes and pathways involved in longevity in Drosophila melanogaster

Jia-qi Li^1,2,
Dan-dan Duan^1,2,
Jian-qin Zhang¹,
Yu-zhi Zhou¹,
Xue-mei Qin¹,
Guan-hua Du^1,3 &
Li Gao¹

Molecular Genetics and Genomics volume 294, pages 1463–1475 (2019)Cite this article

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Abstract

The pursuit of longevity has been the goal of humanity since ancient times. Genetic alterations have been demonstrated to affect lifespan. As increasing numbers of pro-longevity genes and anti-longevity genes have been discovered in Drosophila, screening for functionally important genes among the large number of genes has become difficult. The aim of the present study was to explore critical genes and pathways affecting longevity in Drosophila melanogaster. In this study, 168 genes associated with longevity in D. melanogaster were collected from the Human Ageing Genomic Resources (HAGR) database. Network clustering analysis, network topological analysis, and pathway analysis were integrated to identify key genes and pathways. Quantitative real-time PCR (qRT-PCR) was applied to verify the expression of genes in representative pathways and of predicted genes derived from the gene–gene sub-network. Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway. Moreover, the results revealed that six key genes in representative pathways, including Cat, Ry, S6k, Sod, Tor, and Tsc1, and the predicted genes Jra, Kay, and Rheb exhibited significant expression changes in ageing D. melanogaster strain w¹¹¹⁸ compared to young ones. Overall, our results revealed that six pathways and six key genes might play pivotal roles in regulating longevity, and three interacting genes might be implicated in longevity. The results will not only provide new insight into the mechanisms of longevity, but also provide novel ideas for network-based approaches for longevity-related research.

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Funding

This project was supported by the National Natural Science Foundation of China (81603319) and was partly supported by the Youth Science and Technology Research Fund of Shanxi Province (201801D221374), the Postgraduate Education Innovation Project (2018SY008), the Science and Technology Innovation Team of Shanxi Province (201605D131045-18), and the Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province (201705D111008-21).

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Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92 Wu Cheng Road, Taiyuan, 030006, People’s Republic of China
Jia-qi Li, Dan-dan Duan, Jian-qin Zhang, Yu-zhi Zhou, Xue-mei Qin, Guan-hua Du & Li Gao
College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, 030006, People’s Republic of China
Jia-qi Li & Dan-dan Duan
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of China
Guan-hua Du

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Jia-qi Li
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Dan-dan Duan
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Jian-qin Zhang
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Yu-zhi Zhou
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Xue-mei Qin
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Guan-hua Du
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Li Gao
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Li, Jq., Duan, Dd., Zhang, Jq. et al. Bioinformatic prediction of critical genes and pathways involved in longevity in Drosophila melanogaster. Mol Genet Genomics 294, 1463–1475 (2019). https://doi.org/10.1007/s00438-019-01589-1

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Received: 14 January 2019
Accepted: 21 June 2019
Published: 20 July 2019
Issue Date: December 2019
DOI: https://doi.org/10.1007/s00438-019-01589-1

Keywords

Drosophila melanogaster
Longevity
Gene
Pathway
Network