Development:Y染色體決定性別?NO!古老性基因或許是性別決定的始祖

2015年4月20日 訊 /生物谷BIOON/ --近日，來自昆士蘭大學的研究者使得哺乳動物的一種「退休」的性基因重新復活過來，使其開啟雄性小鼠的發育；這種名為Dmrt1的基因雖然不會被哺乳動物用來確定性別，但其卻在決定許多脊椎動物的性別上扮演著重要的角色，比如青蛙、魚類及鳥類等；相關研究為揭開決定人類和動物性別的基因的進化提供了新的研究線索和思路。

研究者Peter說道，Dmrt1是一種古老的遺傳遺蹟，科學家們認為該基因在哺乳動物的性別決定中失去了應有的功能，而如今現代哺乳動物的性別則是由Y染色體上基因變體來確定的。當功能性基因被替換角色後，比如Dmrt1被Y染色體上的性別決定區所替代，我們就可以假設這是因為原始的基因失去了自身的功能或者其並不在合適的時間及地點被表達所致。

當這一切發生時，我們機體就會阻斷維護這些基因的功能，最終這種失去功能的基因就會退休，或者其有可能獲取新的功能；從理論上來講Dmrt1基因你就好比是一臺古老的、沒有維護的割草機放在小屋落滿灰塵一樣，然而讓研究者比較驚奇的是，當將割草機（Dmrt1）推出小屋其就會重新獲得完整的功能，這一點讓人非常不可思議。

文章中研究者Liang Zhao表示，我們通過過表達基因Dmrt1就可以實現雌性向雄性的完全成功逆轉；目前在哺乳動物中被認為有一些基因可以決定性別，而如今我們也可以將Dmrt1基因加入到這個性別決定的重要群組中。從進化學角度來講，新基因接替老基因後，老基因就會退休但是當其處於合適的時間及位置時候其仍然會履行自己之前的功能或角色。

研究者希望本文研究可以幫助科學家們在農業、害蟲等研究領域帶來幫助，比如管理害蟲的性別比率等，相關研究刊登於國際雜誌Development上，由澳大利亞研究委員會等機構提供資助。（生物谷Bioon.com）

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Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1.

Zhao L1, Svingen T1, Ng ET1, Koopman P2.

Genes related to Dmrt1, which encodes a DNA-binding DM domain transcription factor, act as triggers for primary sex determination in a broad range of metazoan species. However, this role is fulfilled in mammals by Sry, a newly evolved gene on the Y chromosome, such that Dmrt1 has become dispensable for primary sex determination and instead maintains Sertoli cell phenotype in postnatal testes. Here, we report that enforced expression of Dmrt1 in XX mouse fetal gonads using a Wt1-BAC transgene system is sufficient to drive testicular differentiation and male secondary sex development. XX transgenic fetal gonads showed typical testicular size and vasculature. Key ovarian markers, including Wnt4 and Foxl2, were repressed. Sertoli cells expressing the hallmark testis-determining gene Sox9 were formed, although they did not assemble into normal testis cords. Other bipotential lineages differentiated into testicular cell types, including steroidogenic fetal Leydig cells and non-meiotic germ cells. As a consequence, male internal and external reproductive organs developed postnatally, with an absence of female reproductive tissues. These results reveal that Dmrt1 has retained its ability to act as the primary testis-determining trigger in mammals, even though this function is no longer normally required. Thus, Dmrt1 provides a common thread in the evolution of sex determination mechanisms in metazoans.