Laboratory for Marine Living Resources and Molecular Engineering, College of Marine Science, Zhejiang Ocean University, 105 Wenhua Road, Zhejiang Province, Zhoushan 316000, PR China.
Fish Shellfish Immunol. 2013 Aug;35(2):448-57. doi: 10.1016/j.fsi.2013.04.043. Epub 2013 May 14.
The innate immune system can recognize non-self through pattern recognition receptors. Toll-like receptors were the best-known members of these receptors, and they could sense, recognize, and bind pathogen-associated molecular patterns. TLRs played an important role in innate immune system and were conserved in both invertebrate and vertebrate lineages. Thereinto, TLR9 could detect unmethylated CpG motifs in dsDNA and was expected to undergo coevolution with its microbial ligands. It was known that aquatic and terrestrial organisms dwelled in different environments which contained different pathogens, and they had to adapt to their local environmental conditions. Therefore, we collected TLR9 genes from invertebrate to vertebrate to further explore whether the huge differences between aquatic and terrestrial environments affected the TLR9s evolution between aquatic and terrestrial organisms. Molecular evolution analysis detected positively selected sites in the ancestral lineages of vertebrates, teleosts, and Perciformes but not in the ancestral lineage of mammals. In PAML, site model revealed that extant mammalian TLR9 genes underwent positive selection. However, the positive selection of extant teleosts appeared primarily in Perciformes in which there were 14 positively selected sites. Among these sites, two of them were located on the amino acid insertions of the leucine-rich repeats which could create DNA binding sites, three were found on the convex surface which might possibly affect the flexibility of the TLR solenoids, and six were located on the β-face of concave surface which contained the ligand-binding sites of the TLR solenoids. In other ML methods, we also found three sites under selection that coincided with the codons identified by M8 and these sites were all located in LRRs. The diverse aquatic and terrestrial environments might possess different pathogens to make the living organisms adapt to their local environmental conditions. The positive selection on LRRs in TLR9s of Perciformes might be associated with the adaptation to the rapidly evolving pathogens in the water.
固有免疫系统可以通过模式识别受体识别非自身。 Toll 样受体是这些受体中最著名的成员，它们可以感知、识别和结合病原体相关的分子模式。 TLRs 在固有免疫系统中发挥着重要作用，并且在无脊椎动物和脊椎动物谱系中都保守。其中，TLR9 可以检测双链 DNA 中的未甲基化 CpG 基序，并且有望与其微生物配体共同进化。已知水生和陆生生物栖息在不同的环境中，这些环境包含不同的病原体，它们必须适应其当地的环境条件。因此，我们从无脊椎动物到脊椎动物收集 TLR9 基因，以进一步探讨水生和陆生环境之间的巨大差异是否影响 TLR9 在水生和陆生生物之间的进化。分子进化分析在脊椎动物、硬骨鱼和鲈形目动物的祖先谱系中检测到正选择位点，但在哺乳动物的祖先谱系中没有检测到。在 PAML 中，位点模型显示，现存的哺乳动物 TLR9 基因经历了正选择。然而，现存硬骨鱼的正选择主要出现在鲈形目动物中，其中有 14 个正选择位点。在这些位点中，有两个位于富含亮氨酸重复序列的氨基酸插入处，可以创建 DNA 结合位点，三个位于凸面，可能会影响 TLR 螺线管的灵活性，六个位于凹面的 β 面，包含 TLR 螺线管的配体结合位点。在其他 ML 方法中，我们还发现了三个受选择的位点与 M8 识别的密码子重合，这些位点都位于 LRRs 中。多样的水生和陆生环境可能拥有不同的病原体，使生物适应其当地的环境条件。鲈形目动物 TLR9 中 LRRs 的正选择可能与对水中快速进化的病原体的适应有关。
