Data_Sheet_3_Evolution of Matrix Gla and Bone Gla Protein Genes in Jawed Vertebrates.DOCX

Matrix Gla protein (Mgp) and bone Gla protein (Bgp) are vitamin-K dependent proteins that bind calcium in their γ-carboxylated versions in mammals. They are recognized as positive (Bgp) or negative (Mgp and Bgp) regulators of biomineralization in a number of tissues, including skeletal tissues of bony vertebrates. The Mgp/Bgp gene family is poorly known in cartilaginous fishes, which precludes the understanding of the evolution of the biomineralization toolkit at the emergence of jawed vertebrates. Here we took advantage of recently released genomic and transcriptomic data in cartilaginous fishes and described the genomic loci and gene expression patterns of the Mgp/Bgp gene family. We identified three genes, Mgp1, Mgp2, and Bgp, in cartilaginous fishes instead of the single previously reported Mgp gene. We describe their genomic loci, resulting in a dynamic evolutionary scenario for this gene family including several events of local (tandem) duplications, but also of translocation events, along jawed vertebrate evolution. We describe the expression patterns of Mgp1, Mgp2, and Bgp in embryonic stages covering organogenesis in the small-spotted catshark Scyliorhinus canicula and present a comparative analysis with Mgp/Bgp family members previously described in bony vertebrates, highlighting ancestral features such as early embryonic, soft tissues, and neuronal expressions, but also derived features of cartilaginous fishes such as expression in fin supporting fibers. Our results support an ancestral function of Mgp in skeletal mineralization and a later derived function of Bgp in skeletal development that may be related to the divergence of bony vertebrates.

基质Gla蛋白（Matrix Gla protein, Mgp）与骨Gla蛋白（bone Gla protein, Bgp）均为维生素K依赖型蛋白，在哺乳动物体内以γ-羧化形式结合钙离子。它们被认为是多种组织（包括硬骨脊椎动物的骨骼组织）中生物矿化的正向（Bgp）或负向（Mgp与Bgp）调控因子。目前学界对软骨鱼类中的Mgp/Bgp基因家族所知甚少，这阻碍了我们对有颌脊椎动物起源时生物矿化工具库演化过程的理解。本研究借助近期公开的软骨鱼基因组与转录组数据，解析了Mgp/Bgp基因家族的基因组位点与基因表达模式。我们在软骨鱼类中鉴定出三个基因，即Mgp1、Mgp2与Bgp，而非此前报道的单个Mgp基因。通过对其基因组位点的分析，我们揭示了该基因家族在有颌脊椎动物演化历程中的动态演化图景，其中包含多次局部（串联）复制事件以及易位事件。本研究以斑点猫鲨（Scyliorhinus canicula）为对象，解析了其器官发生阶段胚胎内Mgp1、Mgp2与Bgp的表达模式，并与此前在硬骨脊椎动物中报道的Mgp/Bgp家族成员开展比较分析，重点凸显了该家族的祖先特征（如早期胚胎、软组织及神经元表达），同时也揭示了软骨鱼类特有的衍生特征，例如在鳍支撑纤维中的表达。本研究结果支持Mgp在骨骼矿化中发挥祖先功能，而Bgp则在骨骼发育中具备较晚演化出的衍生功能，这一功能可能与硬骨脊椎动物的分化相关。