Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, College of Aquaculture and Life Science, Shanghai Ocean University, Shanghai, 201306, China.
Shanghai Engineering Research Center of Aquaculture, Shanghai Ocean University, Shanghai, 201306, China.
Mol Genet Genomics. 2021 May;296(3):665-676. doi: 10.1007/s00438-021-01773-2. Epub 2021 Mar 14.
Complement C9, as a member of terminal complement component (TCC) protein, plays important roles in innate immunity. However, some complement components appear to show difference and evolutionary complexity between higher and lower vertebrates. Hence, it is essential to carry on a study of evolutionary origin and systematic function of C9 in fish and non-fish vertebrates. This study aims to explore the complement gene evolution and potential function in fish based on molecular and structural biology. Herein, we found complete divergence of C9 throughout the gene evolution. The optimal codons of C9 sequences tended to be closer to the genomes of lower vertebrates compared to higher vertebrates. Further, conserved amino acids in the C9 TMH1 region were identified, implying their potential functional association with MAC growth and pore formation. Transposons and simple repeats, as gene elements, exhibited a differential distribution in the genomic regions in different animal groups but were sparsely scattered around the sixth exon (TMH1 region). Notably, this demonstrated the regulatory complexity of the C9 gene in higher vertebrates. The negative selection pressures on fish and non-fish groups improved both the sequence conservation and similarity. Through gene/protein regulatory network and pathway analyses, the systematic function of C9 protein was showcased; thus, we could reveal the divergence of the systematic function of C9 across species from different evolutionary positions. In addition, more complicated functions of C9 in higher vertebrates could established by the altered spatial conformation of the protein. Collectively, the present study illustrates the C9 gene evolutionary process and the difference in its systematic function across multiple species. Such advances provide new insights for understanding the evolutionary and potential functions of complement C9.
补体 C9 作为末端补体成分 (TCC) 蛋白的一员，在先天免疫中发挥着重要作用。然而，一些补体成分在高等和低等脊椎动物之间似乎表现出差异和进化复杂性。因此，有必要对鱼类和非鱼类脊椎动物中 C9 的进化起源和系统功能进行研究。本研究旨在基于分子和结构生物学探索鱼类补体基因的进化和潜在功能。在此，我们发现 C9 基因在整个进化过程中完全分化。与高等脊椎动物相比，C9 序列的最优密码子更倾向于接近低等脊椎动物的基因组。此外，还鉴定了 C9 TMH1 区域的保守氨基酸，暗示它们可能与 MAC 生长和孔形成具有潜在的功能关联。转座子和简单重复序列作为基因元件，在不同动物群体的基因组区域中表现出不同的分布，但在第六外显子（TMH1 区域）周围稀疏分布。值得注意的是，这表明 C9 基因在高等脊椎动物中的调控复杂性。鱼类和非鱼类群体的负选择压力提高了序列的保守性和相似性。通过基因/蛋白质调控网络和途径分析，展示了 C9 蛋白的系统功能；因此，我们可以揭示不同进化位置的物种中 C9 系统功能的分化。此外，通过改变蛋白质的空间构象，可以建立 C9 在高等脊椎动物中更复杂的功能。总之，本研究说明了 C9 基因的进化过程及其在多种物种中的系统功能差异。这些进展为理解补体 C9 的进化和潜在功能提供了新的视角。
