Elucidation of de novo gene birth and pseudogenization processes via reconstruction of ancestral transcriptional regulation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: HARA Yuichiro 公益財団法人東京都医学総合研究所, ゲノム医学研究センター, 主席研究員 (70709708)
• Co-Investigator(Kenkyū-buntansha): 吉沢 直子 (須賀田直子) 公益財団法人東京都医学総合研究所, ゲノム医学研究センター, 主席研究員 (30344071)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: de novo遺伝子 / 偽遺伝子 / 超並列レポーターアッセイ / プロモーター / エンハンサー / 祖先配列

Outline of Final Research Achievements

We elucidated whether protein coding regions or transcription regulatory sites have mainly driven gene evolution in the process of gene birth and loss. To achieve this, we reconstructed the ancestral gene regulation activities of the de novo genes and pseudogenes that occurred in the primate lineage leading to humans. We measured the transcription regulatory activities of the ancestral promoters and enhancers of these genes, which had been difficult to infer in silico, by employing the massively parallel reporter assay with synthesized nucleotide sequences. This study provides a new perspective on the collaborative evolution of transcriptional regulation with the open reading frames in gene birth and death that have been considered primarily only in terms of protein coding regions.

Free Research Field

進化生物学

Academic Significance and Societal Importance of the Research Achievements

これまで困難であった祖先遺伝子の機能を実験的かつ網羅的に復元するアプローチは、進化学ひいてはゲノム科学の根源的な問いでもある転写制御と遺伝子の共役的な進化過程を解明する基盤として、先駆性を持って確立されると期待できる。進化生物学においては、重複遺伝子の多様化やがんゲノム進化など転写制御活性の変化とも共役し得る遺伝子進化を紐解くにあたり、進化時間に沿って転写制御活性を計測するという方法論を確立した。