Accumulating evidence supports the crucial role intestinal microbiota and their metabolites play in the homeostasis of organisms. An important class of metabolites that have been shown to affect the immune system are short chain fatty acids (SCFAs). These SCFAs can affect the host cells via passive diffusion or via ligation to receptors, among others G-protein coupled receptor (GPR) 41 and 43. GPR41 and GPR43 are both part of a family of GPR40-related receptors. Mammalian studies have shown an important role for GPR41 and GPR43 in the modulation of immune responses by SCFAs. However, up till date, no validated coding sequences for orthologues of these SCFA receptors have been published for teleost fish. We used genomic resources and cDNA cloning, to identify and validate ten coding sequences for gpr40L genes in common carp. Phylogenetic analysis showed a division into three subclasses, putatively named class a, b and c, and showed the common carp genes had a closer phylogenetic relationship to mammalian GPR43 than to mammalian GPR41. Synteny analysis revealed a clear conservation of syntenic relationships between gpr40L in the genomes of spotted gar and common carp with the relevant region in the human genome. This conservation of synteny validates the genes identified, as gpr40L. Finally, presence of gpr40L genes was investigated in silico for genomes of 25 different, mostly teleost, fish species largely confirming the observations for gpr40L of common carp with regards to both, subdivision in three subclasses a-c and conservation of synteny. Our data provide an important first step towards an understanding of the role and function of receptors for SCFAs and immunomodulation in fish.

越来越多的证据支持肠道微生物群及其代谢物在生物体稳态中的关键作用。已显示影响免疫系统的一类重要代谢物是短链脂肪酸 (SCFA)。这些 SCFA 可以通过被动扩散或通过与受体的连接影响宿主细胞，其中包括 G 蛋白偶联受体 (GPR) 41 和 43。GPR41 和 GPR43 都是 GPR40 相关受体家族的一部分。哺乳动物研究表明 GPR41 和 GPR43 在调节 SCFAs 的免疫反应中具有重要作用。然而，迄今为止，尚未针对硬骨鱼发表这些 SCFA 受体直系同源物的有效编码序列。我们使用基因组资源和 cDNA 克隆来识别和验证gpr40L的十个编码序列鲤鱼的基因。系统发育分析显示分为三个亚类，假定命名为 a、b 和 c 类，并表明鲤鱼基因与哺乳动物 GPR43 的系统发育关系比与哺乳动物 GPR41 更密切。同线性分析揭示了斑鳢和鲤鱼基因组中的gpr40L与人类基因组中的相关区域之间存在明显的同线性关系。这种同线性的保守性验证了鉴定为gpr40L的基因。最后，在计算机中研究了gpr40L基因的存在，用于 25 种不同的基因组，主要是硬骨鱼，很大程度上证实了gpr40L的观察结果鲤鱼的两个方面，分为三个亚类 ac 和同线性保护。我们的数据为了解短链脂肪酸受体的作用和功能以及鱼类的免疫调节迈出了重要的第一步。