Sex determination in animals is not only determined by karyotype but can also be modulated by environmental cues like temperature via unclear transduction mechanisms. Moreover, in contrast to earlier views that sex may exclusively be determined by either karyotype or temperature, recent observations suggest that these factors rather co-regulate sex, posing another mechanistic mystery. Here, we discovered that certain wild-isolated and mutant C. elegans strains displayed genotypic germline sex determination (GGSD), but with a temperature-override mechanism. Further, we found that BiP, an ER chaperone, transduces temperature information into a germline sex-governing signal, thereby enabling the coexistence of GGSD and temperature-dependent germline sex determination (TGSD). At the molecular level, increased ER protein-folding requirements upon increased temperatures lead to BiP sequestration, resulting in ERAD-dependent degradation of the oocyte fate-driving factor, TRA-2, thus promoting male germline fate. Remarkably, experimentally manipulating BiP or TRA-2 expression allows to switch between GGSD and TGSD. Physiologically, TGSD allows C. elegans hermaphrodites to maintain brood size at warmer temperatures. Moreover, BiP can also influence germline sex determination in a different, non-hermaphroditic nematode species. Collectively, our findings identify thermosensitive BiP as a conserved temperature sensor in TGSD, and provide mechanistic insights into the transition between GGSD and TGSD.

中文翻译：

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鉴定 BiP 作为介导线虫中温度诱导的种系性逆转的温度传感器。


动物的性别决定不仅由核型决定，还可以通过不清楚的转导机制受到温度等环境因素的调节。此外，与早期认为性别可能完全由核型或温度决定的观点相反，最近的观察表明这些因素相当共同调节性别，从而提出了另一个机制之谜。在这里，我们发现某些野生分离和突变的秀丽隐杆线虫菌株表现出基因型种系性别决定（GGSD），但具有温度覆盖机制。此外，我们发现 BiP（一种 ER 伴侣）可将温度信息转换为种系性别控制信号，从而使 GGSD 和温度依赖性种系性别决定 (TGSD) 共存。在分子水平上，随着温度升高，ER 蛋白折叠需求增加，导致 BiP 隔离，导致卵母细胞命运驱动因子 TRA-2 发生 ERAD 依赖性降解，从而促进雄性种系命运。值得注意的是，通过实验操作 BiP 或 TRA-2 表达可以在 GGSD 和 TGSD 之间切换。从生理学角度来说，TGSD 使得线虫雌雄同体能够在较高的温度下保持雏鸟的大小。此外，BiP 还可以影响不同的非雌雄同体线虫物种的种系性别决定。总的来说，我们的研究结果将热敏 BiP 确定为 TGSD 中的保守温度传感器，并为 GGSD 和 TGSD 之间的转变提供了机制见解。