Exploration of gene regulatory systems rewired by mammalian transposable elements.

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K19424
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Ecology and Evolution (including anthropology), and related fields
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Nishihara Hidenori 東京工業大学, 生命理工学院, 助教 (10450727)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: 転移因子 / 哺乳類 / 乳腺

Outline of Final Research Achievements

This study revealed that transposable elements such as retroposons amplified the seed sequences for cis-regulatory elements involved in mammalian morphological evolution by increasing binding sites for various transcription factors. In particular, one-third of the enhancers to which transcriptional activators essential for mammary gland formation bind were derived from transposable elements. These were caused by the two-phased amplifications of retroposons in the common ancestors of eutherians and simian primates. Thus, retroposon-mediated functional sequence expansion contributed profoundly to the common mammalian morphological evolution. Through this study, it was shown that transposable elements had a significant impact on the evolution of large-scale gene regulatory mechanisms.

Free Research Field

ゲノム進化学

Academic Significance and Societal Importance of the Research Achievements

一般に転写活性化因子の結合サイトの新規獲得は単純な塩基置換の蓄積で説明されることが多い。転移因子がゲノム中で数万コピーもの結合サイトを増幅する可能性は以前から指摘されていたが、生物進化におけるその寄与の程度は分かっていなかった。今回その割合とともに哺乳類共通の形態進化に関わるシス調節配列の増大に寄与したことを初めて明らかにした。これにより発現調節ネットワークの改変とそれに伴う形態進化には従来考えられてきたような塩基置換だけでなく転移因子の増幅が深く関係することが明らかになり、今後転移因子の存在意義と生物進化における影響を再考する上で極めて重要な知見となった。