Two divergent leptin paralogues in zebrafish (Danio rerio) that originate early in teleostean evolution

Two divergent leptin paralogues in zebrafish (Danio rerio) that originate early in teleostean evolution
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DOI:
10.1677/joe-09-0034
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发表时间:
2009-06-01
影响因子:
4
通讯作者:
Huising, Mark O.
Huising, Mark O.
中科院分区:
医学2区
文献类型:
--
作者:
Gorissen, Marnix;Bernier, Nicholas J.;Huising, Mark O.

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我们描述了重复的瘦素基因在斑马鱼(Danio rerio),共享只有24%的氨基酸同一性,彼此只有18%与人类瘦素。我们还能够检索到青鳉(青鳉)的第二个瘦素基因。在这两个远亲硬骨鱼类中存在重复的瘦素基因表明,重复的瘦素基因是硬骨鱼类的一个共同特征。尽管一级序列保守性较低,但出于多种原因,我们有信心在哺乳动物和斑马鱼瘦蛋白之间分配同源性。首先,这两种斑马鱼leptins共享其特征性基因结构,并显示与哺乳动物leptin基因保守同线性的关键特征。其次,半胱氨酸残基构成瘦素的单二硫桥在哺乳动物和斑马鱼瘦素中是等间隔的,并且在I类螺旋细胞因子家族的所有成员中是独特的。第三,斑马鱼leptins与其他鱼类leptins和哺乳动物leptins的系统发育聚类分析,由较高的bootstrap值支持。在瘦素簇内,瘦素-b与青鳉的瘦素-b直向同源物形成一个单独的分支。最后,我们的预测的三级结构表明,这两个瘦素符合典型的四个α-螺旋束结构的I类α-螺旋细胞因子。斑马鱼瘦素的差异表达;肝脏显示高瘦素-a表达(与我们观察到的鲤鱼瘦素一致),而瘦素-b表达水平低得多,禁食后进一步下调。在硬骨鱼类中发现重复的瘦素基因增加了我们对早期脊椎动物谱系中瘦素生理学进化的理解。内分泌学杂志(2009)201,329 - 339
We describe duplicate leptin genes in zebrafish (Danio rerio) that share merely 24% amino acid identity with each other and only 18% with human leptin. We were also able to retrieve a second leptin gene in medaka (Oryzias latipes). The presence of duplicate leptin genes in these two distantly related teleosts suggests that duplicate leptin genes are a common feature of teleostean fishes. Despite low primary sequence conservation, we are confident in assigning orthology between mammalian and zebrafish leptins for several reasons. First, both zebrafish leptins share their characteristic gene structure and display key features of conserved synteny with mammalian leptin genes. Secondly, the cysteine residues chat make up leptin's single disulphide bridge are equally spaced in mammalian and zebrafish leptins and are unique among all members of the class-I helical cytokine family. Thirdly, the zebrafish leptins cluster with other fish leptins and mammalian leptins in phylogenetic analysis, supported by high bootstrap values. Within the leptin cluster, leptin-b forms a separate clade with the leptin-b orthologue from medaka. Finally, our prediction of the tertiary structures shows that both leptins conform to the typical four alpha-helix bundle structure of the class-I alpha-helical cytokines. The zebrafish leptins are differentially expressed; the liver shows high leptin-a expression (in concordance with what we observed for carp leptins), while leptin-b is expressed at much lower levels, which are downregulated further upon fasting. The finding of duplicate leptin genes in teleosts adds to our understanding of the evolution of leptin Physiology in the early vertebrate lineage. Journal of Endocrinology (2009) 201, 329-339