Verification of the subfunctionalization hypothesis in paralogous genes by engrafting cis-regulatory elements

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02543
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 45020:Evolutionary biology-related
• Research Institution: Nagoya University (2022-2023); Institute of Physical and Chemical Research (2021)
• Principal Investigator: Sumiyama Kenta 名古屋大学, 生命農学研究科, 教授 (00370114)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 発現制御進化 / ゲノム編集 / cis-element / Dlx遺伝子群 / エンハンサーノックイン

Outline of Final Research Achievements

Mice lacking the pharyngeal arch enhancer of the Dlx5-6 gene cluster by genome editing exhibit a phenotype in which the mandible is transformed into an upper jaw. This result indicates that the Dlx5-6 pharyngeal arch enhancer plays an essential role in mandible development. knock-in of the Dlx5-6 pharyngeal enhancer resulted in an approximately 2-fold increase in Dlx3 expression. mice lacking the Dlx5-6 pharyngeal enhancer were transfected with the Dlx3-4 gene cluster. Crossing the Dlx5-6 pharyngeal enhancer knock-in to the Dlx3-4 gene cluster resulted in mice in which both were homozygous; the phenotype of mice lacking the Dlx5-6 pharyngeal arch enhancer, in which the mandible becomes maxillary and postnatal lethality occurs, was rescued in these mice. These results indicate that paralogous gene function can be transferred to another paralogous gene by enhancer integration.

Free Research Field

進化発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

エンハンサーのノックインにより、内在性遺伝子の既存エンハンサー機能に影響を与えることなく、新しいエンハンサー機能を遺伝子に追加することが可能であることを示すことができた。このことにより複数の異種エンハンサーを一遺伝子に統合することが可能であるということを明らかにした。エンハンサーを移植するというこの手法は、エンハンサー主導の進化メカニズムの理解に役立つだけでなく、家畜などの有用動物の開発や、ヒトの遺伝子治療などに応用できる可能性がある。