哺乳類の調節進化過程におけるトランス作用回路の保存

Andrew B Stergachis¹, Shane Neph¹, Richard Sandstrom¹

¹Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.

Nature

|November 21, 2014

まとめ

哺乳類の遺伝子調節は,主に cis調節要素ではなく,トランス調節回路の変化によって進化する. これは,重要なセルラーネットワークアーキテクチャを維持しながら,規制の可塑性を可能にします.

科学分野:

ゲノミクスゲノミクスとは
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.

背景:

哺乳類の進化は,保存された身体計画を示しているが,遺伝子の制約は限られている.
規制の進化を理解するには,シス作用因子とトランス作用因子を区別する必要があります.

研究の目的:

哺乳類の調節進化に対するシス対トランス作用の貢献を定量化するために.
マウスとヒトのトランスクリプション因子結合の景観を比較する.

主な方法:

25種類のマウスの細胞/組織でゲノムDNase Iの足跡.
核酸分解能トランスクリプション因子占有部位の800万個を特定しました.
マウスとヒトの転写因子の足跡と規制ネットワークの比較分析.

主要な成果:

マウスとヒトの転写因子の足跡は,規制用辞書において ~95%の類似性を共有しています.
マウスの転写因子足跡の約20%にのみ,ヒトのオートロロジがあるため,シス調節的ターンオーバーを示しています.
シス・ランドスケープの変化にもかかわらず,対対の規制相互作用の約50%は進化的イノベーションによって保存されています.
転写因子接続の細胞ネットワークアーキテクチャは,マウスと人間の間で高度に保存されています.

結論:

哺乳類の遺伝子調節に関する進化的選択は,トランス調節回路を標的とする.
このターゲティングは,コアネットワーク機能を保持しながら,Cis規制の可塑性を可能にします.
保存された規制ネットワークは,転写因子認識配列の適応的進化によって維持されます.

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