Institute of Molecular Ecology and Evolution, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, China.
Mol Biol Evol. 2011 Feb;28(2):1025-31. doi: 10.1093/molbev/msq286. Epub 2010 Oct 29.
For the past 50 years, it was believed that all bats, like humans and guinea pigs, did not synthesize vitamin C (Vc) because they lacked activity of L-gulonolactone oxidase (GULO) in their livers. Humans and guinea pigs lack the activity due to pseudogenization of GULO in their genomes, but there is no genetic evidence to show whether such loss in bats is caused by pseudogenization. Unexpectedly, our successful molecular cloning in one frugivorous bat (Rousettus leschenaultii) and one insectivorous bat (Hipposideros armiger) ascertains that no pseudogenization occurs in these species. Furthermore, we find normal GULO protein expression using bat-specific anti-GULO polyclonal antibodies in bats, evaluated by Western blotting. Most surprisingly, GULO activity assays reveal that these two bat species have retained the ability to synthesize Vc, but at low levels compared with the mouse. It is known that bats in the genus Pteropus have lost GULO activity. We then found that functional constraints acting on the GULO of Pteropus vampyrus (which lost its function) are relaxed. These results imply that the ability to synthesize Vc in bats has not been lost completely in species as previously thought. We also suggest that the evolution of bat GULO genes can be a good model to study genetic processes associated with loss-of-function.
在过去的 50 年里，人们一直认为所有蝙蝠，如人类和豚鼠一样，不能合成维生素 C（Vc），因为它们的肝脏缺乏 L-古洛糖酸内酯氧化酶（GULO）的活性。人类和豚鼠由于基因组中 GULO 的假基因化而缺乏这种活性，但没有遗传证据表明蝙蝠的这种缺失是由假基因化引起的。出乎意料的是，我们在一种食果蝙蝠（Rousettus leschenaultii）和一种食虫蝙蝠（Hipposideros armiger）中成功地进行了分子克隆，确定这些物种中没有发生假基因化。此外，我们使用蝙蝠特异性抗 GULO 多克隆抗体通过 Western blot 评估，发现蝙蝠中存在正常的 GULO 蛋白表达。最令人惊讶的是，GULO 活性测定显示，这两种蝙蝠物种仍然具有合成 Vc 的能力，但与小鼠相比，其能力较低。已知在 Pteropus 属中蝙蝠已经失去了 GULO 活性。然后，我们发现作用于 Pteropus vampyrus 的 GULO 的功能约束（其失去了功能）被放松了。这些结果表明，以前认为蝙蝠合成 Vc 的能力在某些物种中并没有完全丧失。我们还建议，蝙蝠 GULO 基因的进化可以成为研究与功能丧失相关的遗传过程的良好模型。
