エピスタティック・ラチェットは,グルココルチコイド受容体の進化の方向を制限する
Jamie T Bridgham1, Eric A Ortlund, Joseph W Thornton
1Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, Oregon 97403, USA.
Nature
|September 26, 2009
まとめ
グルココルチコイド受容体のホルモン特異性など,タンパク質機能の進化的変化は,不可逆的になる可能性があります. 後の突然変異は新しい機能を最適化するが,祖先の状態への帰還を阻害し,タンパク質の進化における歴史的偶然性を強調する.
科学分野:
- 進化生物学の進化生物学について
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- 進化の可逆性,特にタンパク質の機能のような複雑な特徴については,生物学において重要な問題である.
- 進化の逆転性に関する以前の研究は,方法論的な課題と機械的理解の欠如によって制限されていました.
- 進化の不可逆性を引き起こす要因を理解することは,生命の歴史と未来を理解するために極めて重要です.
研究 の 目的:
- 特定のケーススタディを使用して,タンパク質の構造と機能における進化的変化の可逆性を調査する.
- 脊椎動物のグルココルチコイド受容体のホルモン特異性における進化的不可逆性のメカニズム的基礎を決定する.
- 進化の軌道の形成における歴史的偶然の役割を評価する.
主な方法:
- 過去のタンパク質の形を再現するための先祖の遺伝子再構築.
- 特定の突然変異を体系的に変化させるためのタンパク質工学.
- タンパク質変異の3次元構造を決定するX線結晶学.
主要な成果:
- グルココルチコイド受容体における新しいホルモンの特異性の進化は,新しい機能を最適化する5つの"制限"変異を伴う.
- これらの制限性突然変異は,祖先の形状に必要なタンパク質構造を不安定化し,直接逆転を非機能的にしました.
- 制限性突然変異の逆転だけでは,祖先の機能を回復させることができず,一方的な進化の経路を示しています.
結論:
- 新しいタンパク質の機能につながる進化の経路は,その後の最適化変異のために進化的にアクセス不能になる可能性があります.
- 観察された"ラッチのような"エピスタシスは,歴史的偶然がタンパク質の進化において重要な役割を果たしていることを示しています.
- タンパク質における複雑な進化的変化の直接的な逆転は,祖先の状態に対する強い選択的圧力下でもありえない.
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