Supplementary Material for: Correlated Evolution of Gonadotropin-Releasing Hormone and Gonadotropin-Inhibitory Hormone and Their Receptors in Mammals

<b><i>Background:</i></b> Evolutionary rate variation in genes (proteins) is manifested both within the species (genome) and between the species (genomes). However, the interdependent components of a biological system in form of a gene or a protein are expected to evolve in a correlated manner under a common functional constraint. <b><i>Methods:</i></b> The phylogenetic analysis and correlation analysis of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) and their receptors (GnRHR and GnIHR) was conducted along with other control neuropeptides. <b><i>Results:</i></b> Both neuropeptides and their receptors regulating the reproductive neuroendocrine axis in vertebrates exhibited a correlated evolution under a common physiological constraint to regulate the release of gonadotropin. This result supports a coordinated substitution of amino acids in the GnRH and the GnIH neuropeptides along with their receptors in terms of similar evolutionary rates and distances with similar nucleotide composition of genes. <b><i>Conclusion:</i></b> This is the first demonstration of the correlated evolution of two components of an endocrine system regulating the release of gonadotropin which are acting in concert for successful reproduction.

<b><i>背景：</i></b> 基因（蛋白质）的进化速率变异既存在于物种种内（基因组内），也存在于物种种间（不同基因组间）。然而，以基因或蛋白质形式存在的生物系统的相互依存组分，在共同的功能约束下，理应以协同方式进行进化。<b><i>方法：</i></b> 本研究对促性腺激素释放激素（gonadotropin-releasing hormone, GnRH）、促性腺激素抑制激素（gonadotropin-inhibitory hormone, GnIH）及其受体（促性腺激素释放激素受体（GnRHR）、促性腺激素抑制激素受体（GnIHR）），连同其他对照神经肽一同开展了系统发育分析与相关性分析。<b><i>结果：</i></b> 调控脊椎动物生殖神经内分泌轴的这两种神经肽及其受体，在调控促性腺激素释放的共同生理约束下，呈现出协同进化模式。该结果表明，促性腺激素释放激素、促性腺激素抑制激素这两种神经肽及其受体的氨基酸替换具有协同性，具体体现为进化速率与进化距离相近，且相关基因的核苷酸组成也具有相似性。<b><i>结论：</i></b> 本研究首次证实，调控促性腺激素释放、协同作用以保障成功繁殖的内分泌系统的两个组分，存在协同进化现象。