Civitello Megan L, Denton Robert, Zasloff Michael A, Malone John H
Institute of Systems Genomics, Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269.
Georgetown University School of Medicine, MedStar Georgetown Transplant Institute, Washington D.C. 20057.
G3 (Bethesda). 2019 Feb 7;9(2):581-589. doi: 10.1534/g3.118.200880.
The skin secretions of many frogs have genetically-encoded, endogenous antimicrobial peptides (AMPs). Other species, especially aposematic poison frogs, secrete exogenously derived alkaloids that serve as potent defense molecules. The origins of these defense systems are not clear, but a novel bile-acid derived metabolite, tauromantellic acid, was recently discovered and shown to be endogenous in poison frogs (, , and ). These observations raise questions about the evolutionary history of AMP genetic elements, the mechanism and function of tauromatellic acid production, and links between these systems. To understand the diversity and expression of AMPs among frogs, we assembled skin transcriptomes of 13 species across the anuran phylogeny. Our analyses revealed a diversity of AMPs and AMP expression levels across the phylogenetic history of frogs, but no observations of AMPs in We examined genes expressed in the bile-acid metabolic pathway and found that (Cytochrome P450), (bile acid-CoA: amino acid N-acyltransferase), and (alpha-methylacyl-CoA racemase) were highly expressed in the skin of and either lowly expressed or absent in other frog species. In particular, catalyzes the first reaction in the cholesterol catabolic pathway and is the rate-limiting step in regulation of bile acid synthesis, suggesting unique activation of the bile acid pathway in skin. The activation of the bile acid pathway in the skin of and the lack of observed AMPs fuel new questions about the evolution of defense compounds and the ectopic expression of the bile-acid pathway.
许多青蛙的皮肤分泌物含有基因编码的内源性抗菌肽（AMPs）。其他物种，特别是具有警戒色的毒蛙，会分泌外源性生物碱，这些生物碱是有效的防御分子。这些防御系统的起源尚不清楚，但最近发现了一种新的胆汁酸衍生代谢物——牛磺曼泰酸，并证明其在毒蛙体内是内源性的（参考文献[具体文献1]、[具体文献2]和[具体文献3]）。这些观察结果引发了关于AMP基因元件的进化历史、牛磺曼泰酸产生的机制和功能以及这些系统之间联系的问题。为了了解青蛙中AMPs的多样性和表达情况，我们在无尾目系统发育中组装了13个物种的皮肤转录组。我们的分析揭示了青蛙系统发育历史中AMPs的多样性和AMP表达水平，但在[具体物种]中未观察到AMPs。我们检查了胆汁酸代谢途径中表达的基因，发现[具体基因1]（细胞色素P450）、[具体基因2]（胆汁酸-CoA：氨基酸N-酰基转移酶）和[具体基因3]（α-甲基酰基辅酶A消旋酶）在[具体物种]的皮肤中高度表达，而在其他蛙类物种中表达低或不表达。特别是，[具体基因1]催化胆固醇分解代谢途径中的第一步反应，是胆汁酸合成调节中的限速步骤，这表明[具体物种]皮肤中胆汁酸途径有独特的激活。[具体物种]皮肤中胆汁酸途径的激活以及未观察到AMPs，引发了关于防御化合物进化和胆汁酸途径异位表达的新问题。
