Functional and evolutionary insights into vertebrate kisspeptin systems from studies of fish brain
Functional and evolutionary insights into vertebrate kisspeptin systems from studies of fish brain
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DOI：
10.1111/j.1095-8649.2009.02496.x
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发表时间：
2010-01-01
影响因子：
2
通讯作者：
Oka, Y.
中科院分区：
文献类型：
--
作者：
Akazome, Y.;Kanda, S.;Oka, Y.
Kiss1 基因产物 Kisspeptin 现在被认为是大多数脊椎动物下丘脑-垂体-性腺 (HPG) 轴的重要调节剂。最近在鱼类中的发现开始为 Kisspeptin 研究奠定了一个新的阶段。最近报道了几种鱼类和两栖动物物种中存在旁系同源 Kisspeptin 基因以及 Kisspeptin 受体（以前称为 GPR54）基因。这些鱼类可以为从进化角度研究脊椎动物 Kisspeptin 和 Kisspeptin 受体系统的一般原理提供极好的动物模型。与迄今为止主要研究的胎盘和有袋哺乳动物物种不同，许多硬骨鱼物种具有kisspeptin的两个旁系同源基因，kiss1和kiss2。青鳉、Oryzias latipes 中的 Kiss1 和 Kiss2 在独特的下丘脑神经元群体中表达，是研究生殖中枢调节的良好模型系统。在这里，kiss1 系统而非 Kiss2 系统显示出表达动态，强烈表明其通过对 GnRH1 神经元的作用直接参与 HPG 轴调节。另一方面，kiss1基因缺失，并且在某些鱼类中仅表达kiss2。此外，最近有一些报告表明 Kiss2 肽可能是某些鱼类繁殖的有效调节剂。脊椎动物的祖先可能已经有两个旁系同源的kiss基因，它们的主要功能是HPG轴调节。在进化过程中保留了两个旁系同源物的物种中，Kiss1 或 Kiss2 主要保留其 HPG 轴调节能力，而另一个则可能承担新的非生殖功能（新功能化）。或者，两个旁系同源物可以在 HPG 轴调节（子功能化）中承担互补的功能。硬骨鱼和四足动物谱系分化后，两个旁系同源物之一，甚至鸟类中的两个旁系同源物都已丢失（退化）或成为假基因（非功能化），但剩余的旁系同源物保留了其原始的 HPG 轴调节功能。对多种形式的 Kisspeptin 受体和相当混杂的配体-受体关系的鉴定导致进一步提出，当一个或两个旁系同源基因在进化过程中丢失或功能分离时，这种混杂性可能是 Kisspeptin 和 Kisspeptin 受体系统在 HPG 轴调节中功能鲁棒性的基础。
The kiss1 gene product kisspeptin is now considered to be an essential regulator of the hypothalamic-pituitary-gonadal (HPG) axis in most vertebrate species. Recent findings in fishes are beginning to set a new stage for the kisspeptin study; the existence of paralogous kisspeptin genes as well as kisspeptin receptor (formerly called GPR54) genes has quite recently been reported in several fish and amphibian species. The fishes may provide excellent animal models for the study of general principles underlying the kisspeptin and kisspeptin receptor systems of vertebrates from the evolutionary viewpoint. Unlike placental and marsupial mammalian species mainly studied so far, many teleost species have two paralogous genes of kisspeptin, kiss1 and kiss2. Medaka, Oryzias latipes, in which kiss1 and kiss2 are expressed in distinctive hypothalamic neuron populations, is a good model system for the study of central regulation of reproduction. Here, the kiss1 system but not the kiss2 system shows expression dynamics strongly indicative of its direct involvement in the HPG axis regulation via its actions on GnRH1 neurons. On the other hand, the kiss1 gene is missing, and only kiss2 is expressed in some fish species. Also, there are some recent reports that Kiss2 peptide may be a potent regulator of reproduction in some fish species. The ancestral vertebrate probably already had two paralogous kiss genes, and their main function was the HPG axis regulation. In the species that retained both paralogues during evolution, either Kiss1 or Kiss2 predominantly retains its ability for the HPG axis regulation, while the other may assume new non-reproductive functions (neofunctionalization). Alternatively, both the paralogues may assume complementary functions in the HPG axis regulation (subfunctionalization). After the divergence of teleost and tetrapod lineages, either one of the two paralogues, or even both in birds, have been lost (degradation) or became a pseudogene (non-functionalization), but the remaining paralogue retained its original function of HPG axis regulation. The identification of multiple forms of kisspeptin receptors and the rather promiscuous ligand-receptor relationships has led to the further proposal that such promiscuousness may be the basis for the functional robustness of kisspeptin and kisspeptin receptor systems in the HPG axis regulation, when one or both paralogous genes are lost or functionally partitioned during evolution.