遺伝子の本質性は,細胞の進化性に関連した定量的な性質である
Gaowen Liu1, Mei Yun Jacy Yong2, Marina Yurieva3
1Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Cell
|December 3, 2015
まとめ
イーストのほとんどの"必須"遺伝子は適応的進化によって克服され,遺伝子の進化性のグラデントを明らかにします. これは,より良い薬物の標的選択のための進化性を含めるために遺伝子本質性を再定義することを示唆しています.
科学分野:
- 遺伝学
- 進化生物学
- システム生物学
背景:
- 遺伝子の本質性は,遺伝子の削除時に細胞の生存能力によって伝統的に定義されています.
- この定義は 遺伝的変化に対応して 適応し進化する 細胞の能力を無視しています
- 適応的進化を理解することは,遺伝子機能の包括的な見方にとって極めて重要です.
研究 の 目的:
- Saccharomyces cerevisiaeにおける重要な遺伝子の進化性を定量的に評価する.
- 重要な遺伝子の削除に適応するメカニズムの調査.
- 遺伝子の本質性について再定義された概念を提案し, 進化性を組み込む.
主な方法:
- 酵母菌における ~1,000の必須遺伝子の削除後の生存を評価するために厳格な遺伝子スクリーンを実施しました.
- 進化した変異株を適応性変異とプロイド性変化に分析した.
- 遺伝子の本質性と進化性のゲノム全体のグラデントを定量化した.
主要な成果:
- 遺伝子の欠損の約9%は適応進化によって克服されました.
- ゲノム全体のグラデーションを特定し, 遺伝子の進化のレベルが変化していることを示した.
- ヌクレオポリン変異体における適応性アヌプロイディを含むプロイディの変化が観察された.
結論:
- 遺伝子の本質性は絶対的ではなく,適応的進化によって影響を受けます.
- 遺伝子の本質性の定量的な再定義は,生存能力と進化可能性の両方を統合する必要があります.
- この改訂された理解は,抵抗性の発生のリスクを減らす治療目標の選択に役立ちます.
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