Evolution of mammalian sex-determining system by insertion of transposons

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22388
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Tachibna Makoto 大阪大学, 生命機能研究科, 教授 (80303915)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 性決定遺伝子

Outline of Final Research Achievements

The mammalian sex-determining gene Sry induces male development. Since its discovery 30 years ago, Sry has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse Sry and a corresponding novel transcript, two-exon Sry (Sry-T). XY mice lacking Sry-T were sex-reversed, and ectopic expression of Sry-T in XX mice induced male development. Sry-T mRNA is expressed similarly to that of canonical single-exon Sry (Sry-S), but SRY-T protein is expressed predominantly, due to the absence of a degron which we identified in the C-terminus of SRY-S. Sry exon2 appears to have evolved recently in mice, through acquisition of retrotransposon-derived coding sequence to replace the degron. Our findings suggest that in nature, SRY-T, not SRY-S, is the bona fide testis-determining factor.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

Sryと呼ばれる遺伝子は、ほ乳類の性を決める（精巣を作る）ために必須です。ヒトを含めたすべてのほ乳類で、Sryはたったひとつのエキソンからなる遺伝子だと考えられていました。今回の私たちの研究は、マウスのSryがふたつのエキソンからなることを証明しました。Sryが発見されてから30年以上も経ちます。私たちの研究成果は、この間にすっと信じられてきた教科書の記載を書き換えるものとなりました。