Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.
Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost.
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DOI：
10.1186/1471-2148-12-137
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发表时间：
2012-08-03
影响因子：
3.4
通讯作者：
Bury NR
中科院分区：
文献类型：
--
作者：
Li Y;Sturm A;Cunningham P;Bury NR
复制的糖皮质激素受体(GR)存在于大多数硬骨鱼中。保留两个GR的进化优势尚不清楚，因为还没有定义亚型特定的功能性状或生理作用。为了确定硬骨鱼中重复GR保留的驱动因素，本研究检测了硬骨鱼血统全基因组复制事件(WGD)事件两侧出现的两个基本鳍鱼分类群的GR，即硬骨鱼世系全基因组复制事件(WGD前)和骨舌形(WGD后)。该研究鉴定出一种赤眼莲GR(ArGR)和两种GR(PbGR1和PbGR2)。系统发育分析表明，ArGR与硬骨鱼GR形成了一个独立的分支。硬骨鱼GR谱系分为两个亚系，每个亚系包含两个P.buhholzi GR中的一个。ArGR、PbGR1和PbGR2都具有DNA结合区锌指之间的9个氨基酸插入，存在于其中一个硬骨鱼GR谱系(GR1)中，而不存在于另一个(GR2)谱系中。PbGR2的剪接变体产生一种缺少这9个氨基酸(PbGR2b)的异构体。皮质醇在体外刺激ArGR、PbGR2b和PbGR1的反式激活活性，与PbGR2b和PbGR1一起，糖皮质激素11-脱氧皮质醇是比皮质醇更有效的激动剂。在反式激活实验中，PbGR2b和PbGR1对激素的敏感性不同，PbGR2b具有较低的EC50值和较大的折叠诱导。两个重复的巴氏对虾GR之间的反式激活活性敏感性的差异表明，在硬骨鱼谱系中，早期就出现了对虾之间潜在的功能差异。鉴于脊椎动物GR功能的多效性，这一发现符合这样的假设，即复制的GR可能通过亚功能化之后的基因共享而保留下来。基鳍鱼类GRs的DNA结合区有一个9个氨基酸的插入片段。然而，缺乏该插入的PbGR2剪接变异体的存在，以及编码其他硬骨鱼GR2的基因中编码这些氨基酸的外显子的丢失，表明在硬骨鱼中选择了两个具有不同DNA结合域结构的受体。
Duplicated glucocorticoid receptors (GR) are present in most teleost fish. The evolutionary advantage of retaining two GRs is unclear, as no subtype specific functional traits or physiological roles have been defined. To identify factors driving the retention of duplicate GRs in teleosts, the current study examined GRs in representatives of two basal ray-finned fish taxa that emerged either side of the teleost lineage whole genome duplication event (WGD) event, the acipenseriform, Acipenser ruthenus, (pre-WGD) and the osteoglossimorph, Pantodon buchholzi, (post-WGD). The study identified a single GR in A. ruthenus (ArGR) and two GRs in P. buchholzi (PbGR1 and PbGR2). Phylogenetic analyses showed that ArGR formed a distinct branch separate from the teleosts GRs. The teleost GR lineage was subdivded into two sublineages, each of which contained one of the two P. buchholzi GRs. ArGR, PbGR1 and PbGR2 all possess the unique 9 amino acid insert between the zinc-fingers of the DNA-binding domain that is present in one of the teleost GR lineages (GR1), but not the other (GR2). A splice variant of PbGR2 produces an isoform that lacked these 9 amino acids (PbGR2b). Cortisol stimulated transactivation activity of ArGR, PbGR2b and PbGR1 in vitro; with PbGR2b and PbGR1, the glucocorticoid 11-deoxycortisol was a more potent agonist than cortisol. The hormone sensitivity of PbGR2b and PbGR1 differed in the transactivation assay, with PbGR2b having lower EC50 values and greater fold induction. The difference in transactivation activity sensitivity between duplicated GRs of P. buchholzi suggests potential functional differences between the paralogs emerged early in the teleost lineage. Given the pleiotropic nature of GR function in vertebrates, this finding is in accordance with the hypothesis that duplicated GRs were potentially retained through subfunctionalisation followed by gene sharing. A 9 amino acid insert in the DNA-binding domain emerged in basal ray-finned fish GRs. However, the presence of a PbGR2 splice variant that lacks this insert, as well as the loss of the exon encoding these amino acids in the genes encoding for other teleost GR2 suggests the selection of two receptors with different DNA-binding domain structures in teleosts.
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影响因子：
64.5
作者：
Bledsoe, RK;Montana, VG;Xu, HE
通讯作者：
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