Li Yishi, Tower John
Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA.
Mol Genet Genomics. 2009 Feb;281(2):147-62. doi: 10.1007/s00438-008-0400-z. Epub 2008 Nov 15.
During Drosophila aging mortality rate increases exponentially and progeny production per animal declines dramatically, correlating with decreased number and division of somatic and germ-line stem cells in the gonads. To search for genes that might promote both longevity and fecundity, a P element transposon (PdL), containing an outwardly directed, doxycycline-inducible promoter was used to generate conditional mutations. Mutant females were screened for increased fecundity at late ages in the presence of doxycycline. Two genes were identified, named hebe (CG1623) and magu (CG2264), that when over-expressed in adult flies could increase life span by approximately 5-30% in both sexes and increase female fecundity at late ages. Transcripts for magu are enriched in the Drosophila stem cell niche region, and magu encodes a protein related to the human SMOC2 regulator of angiogenesis. While moderate over-expression of magu in adult females increased fecundity at late ages, high-level over-expression of magu was maternal-effect lethal. The data demonstrate that adult-specific over-expression of hebe and magu can increase life span and modulate female fecundity, and provide further evidence against obligatory trade-offs between reproduction and longevity.
在果蝇衰老过程中,死亡率呈指数增长,每只动物的后代产量急剧下降,这与性腺中体细胞和生殖系干细胞数量及分裂的减少相关。为了寻找可能同时促进长寿和繁殖力的基因,使用了一个含有向外定向、强力霉素诱导型启动子的P元素转座子(PdL)来产生条件性突变。在强力霉素存在的情况下,对突变雌性果蝇在老龄时的繁殖力增加情况进行筛选。鉴定出了两个基因,分别命名为赫柏(CG1623)和马古(CG2264),当它们在成年果蝇中过表达时,可使两性的寿命延长约5 - 30%,并增加老龄雌性果蝇的繁殖力。马古的转录本在果蝇干细胞生态位区域富集,且马古编码一种与人类血管生成调节因子SMOC2相关的蛋白质。虽然成年雌性果蝇中适度过表达马古可增加老龄时的繁殖力,但马古的高水平过表达具有母性效应致死性。数据表明,赫柏和马古在成年特异性过表达可延长寿命并调节雌性繁殖力,为繁殖和长寿之间不存在必然权衡提供了进一步证据。