CatSper is a sperm-specific calcium ion (Ca2+) channel, which regulates sperm flagellar beating by tuning cytoplasmic Ca2+ concentrations. Although this Ca2+ channel is essential for mammalian fertilization, recent bioinformatics analyses have revealed that genes encoding CatSper are heterogeneously distributed throughout the eukaryotes, including vertebrates. As this channel is activated by cytoplasmic alkalization in mammals and sea urchins, it has been proposed that the sperm-specific Na+/H+ exchanger (sNHE, a product of the SLC9C gene family) positively regulates its activity. In mouse, sNHE is functionally coupled to soluble adenylyl cyclase (sAC). CatSper, sNHE, and sAC have thus been considered functionally interconnected in the control of sperm motility, at least in mouse and sea urchin. We carried out a comparative genomic analysis to explore phylogenetic relationships among CatSper, sNHE and sAC in eukaryotes. We found that sNHE occurs only in Metazoa, although sAC occurs widely across eukaryotes. In animals, we found correlated and restricted distribution patterns of the three proteins, suggesting coevolution among them in the Metazoa. Namely, nearly all species in which CatSper is conserved also preserve sNHE and sAC. In contrast, in species without sAC, neither CatSper nor sNHE is conserved. On the other hand, the distribution of another testis-specific NHE (NHA, a product of the SLC9B gene family) does not show any apparent association with that of CatSper. Our results suggest that CatSper, sNHE and sAC form prototypical machinery that functions in regulating sperm flagellar beating in Metazoa. In non-metazoan species, CatSper may be regulated by other H+ transporters, or its activity might be independent of cytoplasmic pH.

中文翻译：

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比较基因组分析表明，精子特异性钠/质子交换器和可溶性腺苷酸环化酶是后生动物中 CatSper 的关键调节因子

CatSper 是精子特异性钙离子 (Ca2+) 通道，通过调节细胞质 Ca2+ 浓度来调节精子鞭毛的跳动。尽管这种 Ca2+ 通道对于哺乳动物受精至关重要，但最近的生物信息学分析表明，编码 CatSper 的基因在整个真核生物（包括脊椎动物）中异质分布。由于该通道在哺乳动物和海胆中被细胞质碱化激活，因此有人提出精子特异性 Na+/H+ 交换器（sNHE，SLC9C 基因家族的产物）正向调节其活性。在小鼠中，sNHE 与可溶性腺苷酸环化酶 (sAC) 功能性偶联。因此，CatSper、sNHE 和 sAC 在控制精子活力方面被认为在功能上是相互关联的，至少在小鼠和海胆中是这样。我们进行了比较基因组分析，以探索真核生物中 CatSper、sNHE 和 sAC 之间的系统发育关系。我们发现 sNHE 仅发生在后生动物中，尽管 sAC 广泛发生在真核生物中。在动物中，我们发现这三种蛋白质的相关且受限的分布模式，表明它们在后生动物中存在共同进化。也就是说，几乎所有保留了 CatSper 的物种也保留了 sNHE 和 sAC。相比之下，在没有 sAC 的物种中，CatSper 和 sNHE 都不保守。另一方面，另一种睾丸特异性 NHE（NHA，SLC9B 基因家族的产物）的分布与 CatSper 的分布没有显示出任何明显的关联。我们的结果表明，CatSper、sNHE 和 sAC 形成了在后生动物中调节精子鞭毛跳动的典型机制。在非后生动物物种中，CatSper 可能受到其他 H+ 转运蛋白的调节，或其活性可能独立于细胞质 p​​H 值。