The Caenorhabditis elegans Female-Like State: Decoupling the Transcriptomic Effects of Aging and Sperm Status

Understanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. Caenorhabditis elegans XX animals are hermaphrodites that exhaust their sperm after 3 d of egg-laying. Even though C. elegans can live for many days after cessation of egg-laying, the molecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism. To study the effects of sperm depletion and aging of C. elegans during the first 6 d of adulthood, we measured the transcriptomes of first-day adult hermaphrodites and sixth-day sperm-depleted adults, and, at the same time points, mutant fog-2(lf) worms that have a feminized germline phenotype. We found that we could separate the effects of biological aging from sperm depletion. For a large subset of genes, young adult fog-2(lf) animals had the same gene expression changes as sperm-depleted sixth-day wild-type hermaphrodites, and these genes did not change expression when fog-2(lf) females reached the sixth day of adulthood. Taken together, this indicates that changing sperm status causes a change in the internal state of the worm, which we call the female-like state. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm. 4 conditions; 3 samples per condition. Young adults are 1d old adults without visible eggs. Aged adults are 6th day adults, post-egg-laying. The fog-2 mutant strain used was JK574

要完整解析整个生物体的基因组与基因功能，我们需要充分掌握所研究生物体的生命周期与生理特征。秀丽隐杆线虫（Caenorhabditis elegans，简称C. elegans）XX型个体为雌雄同体，其在产卵3天后便会耗尽自身精子。即便秀丽隐杆线虫在停止产卵后仍可存活多日，但该状态下的分子生理特征并未如生命周期其他阶段那般得到深入研究，尽管已有文献报道其行为与代谢发生了改变。为探究成年秀丽隐杆线虫成长至头6天期间，精子耗尽与衰老对其产生的影响，我们分别对成年首日的雌雄同体个体、第六日精子耗尽的野生型个体，以及同一时间点下携带雌性化生殖系表型的fog-2(lf)突变蠕虫进行了转录组（transcriptome）测序。研究发现，我们能够将生物衰老与精子耗尽的影响区分开来。对于大量基因子集而言，成年首日的fog-2(lf)突变体其基因表达变化模式与第六日精子耗尽的野生型雌雄同体个体一致；且当fog-2(lf)突变体生长至成年第六天时，这些基因的表达并未发生改变。综上，这表明精子状态的改变会引发蠕虫体内生理状态发生变化，我们将该状态命名为类雌性状态（female-like state）。本研究数据清晰呈现了秀丽隐杆线虫早期衰老过程中全基因组基因表达的整体变化图景。本实验共设置4种实验条件，每组条件设置3个生物学重复样本。年轻成虫为未观察到卵的1日龄成虫；衰老成虫为完成产卵后的6日龄成虫。本研究使用的fog-2突变菌株为JK574。