Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebrates

Abstract SIRT6, a member of the sirtuin protein family, is recognized as a tumor suppressor. This study investigates the evolutionary history of the SIRT gene family and examines the selective pressures shaping their functional divergence. Insights into the evolution of these genes may enhance our u...

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Main Authors: Qiuxi Zhou, Xiongtao Yang, Da Li, Jing Li, Ling Peng, Wenwu He
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85344-0
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author Qiuxi Zhou
Xiongtao Yang
Da Li
Jing Li
Ling Peng
Wenwu He
author_facet Qiuxi Zhou
Xiongtao Yang
Da Li
Jing Li
Ling Peng
Wenwu He
author_sort Qiuxi Zhou
collection DOAJ
description Abstract SIRT6, a member of the sirtuin protein family, is recognized as a tumor suppressor. This study investigates the evolutionary history of the SIRT gene family and examines the selective pressures shaping their functional divergence. Insights into the evolution of these genes may enhance our understanding of their roles in disease pathology. Seventy-three amino acid sequences and full-length mRNA sequences from 22 vertebrate species and one invertebrate were retrieved from public databases. Phylogenetic relationships among the seven SIRT gene family members were reconstructed using Bayesian inference. Codon-based models were applied to detect site-specific positive selection, and likelihood ratio tests (LRTs) were used to compare model fits. Positively selected sites were identified using Bayesian empirical Bayes (BEB) methods. Phylogenetic analysis revealed that the seven SIRT gene family members in vertebrates originated from gene duplication events. Asymmetric evolutionary rates and natural selection were identified as the primary drivers of SIRT gene divergence. Eleven positively selected sites (23I, 310 S, 311I, 313 A, 316 K, 320 C, 321 A, 322Q, 323 H, 327E, 328P) were identified with high confidence (posterior probability ≥ 99%), suggesting critical roles in functional divergence. The evolution of the SIRT gene family is characterized by gene duplication and natural selection. The reconstructed phylogenetic tree elucidates the relationships among the seven members, with SIRT6 emerging as a key evolutionary node. Positively selected sites identified in this study may represent mutation hotspots, providing potential targets for future cancer therapy research.
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spelling doaj-art-c27173d2dee34b21bc8a8176835e4c3b2025-01-05T12:19:06ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-85344-0Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebratesQiuxi Zhou0Xiongtao Yang1Da Li2Jing Li3Ling Peng4Wenwu He5Department of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of ChinaDepartment of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of ChinaDepartment of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of ChinaDepartment of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of ChinaDepartment of General Internal Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of ChinaDepartment of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of ChinaAbstract SIRT6, a member of the sirtuin protein family, is recognized as a tumor suppressor. This study investigates the evolutionary history of the SIRT gene family and examines the selective pressures shaping their functional divergence. Insights into the evolution of these genes may enhance our understanding of their roles in disease pathology. Seventy-three amino acid sequences and full-length mRNA sequences from 22 vertebrate species and one invertebrate were retrieved from public databases. Phylogenetic relationships among the seven SIRT gene family members were reconstructed using Bayesian inference. Codon-based models were applied to detect site-specific positive selection, and likelihood ratio tests (LRTs) were used to compare model fits. Positively selected sites were identified using Bayesian empirical Bayes (BEB) methods. Phylogenetic analysis revealed that the seven SIRT gene family members in vertebrates originated from gene duplication events. Asymmetric evolutionary rates and natural selection were identified as the primary drivers of SIRT gene divergence. Eleven positively selected sites (23I, 310 S, 311I, 313 A, 316 K, 320 C, 321 A, 322Q, 323 H, 327E, 328P) were identified with high confidence (posterior probability ≥ 99%), suggesting critical roles in functional divergence. The evolution of the SIRT gene family is characterized by gene duplication and natural selection. The reconstructed phylogenetic tree elucidates the relationships among the seven members, with SIRT6 emerging as a key evolutionary node. Positively selected sites identified in this study may represent mutation hotspots, providing potential targets for future cancer therapy research.https://doi.org/10.1038/s41598-025-85344-0SIRT familyPhylogenetic analysisPositive selectionNatural selectionVertebrates
spellingShingle Qiuxi Zhou
Xiongtao Yang
Da Li
Jing Li
Ling Peng
Wenwu He
Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebrates
Scientific Reports
SIRT family
Phylogenetic analysis
Positive selection
Natural selection
Vertebrates
title Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebrates
title_full Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebrates
title_fullStr Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebrates
title_full_unstemmed Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebrates
title_short Phylogenetic analysis and detection of positive selection in the SIRT gene family across vertebrates
title_sort phylogenetic analysis and detection of positive selection in the sirt gene family across vertebrates
topic SIRT family
Phylogenetic analysis
Positive selection
Natural selection
Vertebrates
url https://doi.org/10.1038/s41598-025-85344-0
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