Evolutionary diversification of the canonical Wnt signaling effector TCF/LEF in chordates.
Evolutionary diversification of the canonical Wnt signaling effector TCF/LEF in chordates.
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DOI：
10.1111/dgd.12771
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发表时间：
2022-04
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--
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WNT信号在动物的发育和再生过程中是必不可少的，但在癌症和糖尿病等疾病中也发挥着重要作用。经典的Wnt信号通路是动物界最保守的信号级联通路之一，T细胞因子/淋巴增强因子(Tcf/LEF)蛋白是Wnt/β-catenin调节基因表达的主要中介。与无脊椎动物相比，脊椎动物具有高度多样性的Tcf/Lef家族基因，这可能是脊椎动物进化起源中Wnt信号的关键变化。然而，人们对这种多元化的确切性质知之甚少。本研究的目的是通过对Tcf/Lef基因结构、分子系统发育和基因同源性的比较研究，阐明脊索动物中Tcf/Lef基因家族之间的同源、同源和异构体关系。我们的结果支持这一观点，即有颌类脊椎动物中的四个TCF/LEF Paralog亚家族是通过早期脊椎动物进化过程中发生的两轮全基因组复制而进化的。重要的是，无颌脊椎动物(环口脊椎动物)TCFs的基因结构比较和共性分析表明，类似TCF7L2的基因结构是祖先脊椎动物结构的密切替代。综上所述，我们提出了一种基于新的前全基因组复制脊椎动物TCF基因模型的详细进化路径。这个祖先基因模型突出了脊索动物和脊椎动物Tcf/LEF基因结构的创新，为理解Wnt/β-catenin信号在脊椎动物进化中的作用提供了基础。典型的Wnt/β-catenin信号通路通过转录因子Tcf/Lef家族发挥作用。本文通过一个新的进化模型描述了在无脊椎动物-脊椎动物转变过程中该家族基因多样性的阶跃变化，该模型包括了在这一转变中推断的中间基因。这为未来研究这些基因在发育和疾病中的功能多样性提供了基础。
Wnt signaling is essential during animal development and regeneration, but also plays an important role in diseases such as cancer and diabetes. The canonical Wnt signaling pathway is one of the most conserved signaling cascades in the animal kingdom, with the T‐cell factor/lymphoid enhancer factor (TCF/LEF) proteins being the major mediators of Wnt/β‐catenin‐regulated gene expression. In comparison with invertebrates, vertebrates possess a high diversity of TCF/LEF family genes, implicating this as a possible key change to Wnt signaling at the evolutionary origin of vertebrates. However, the precise nature of this diversification is only poorly understood. The aim of this study is to clarify orthology, paralogy, and isoform relationships within the TCF/LEF gene family within chordates via in silico comparative study of TCF/LEF gene structure, molecular phylogeny, and gene synteny. Our results support the notion that the four TCF/LEF paralog subfamilies in jawed vertebrates (gnathostomes) evolved via the two rounds of whole‐genome duplications that occurred during early vertebrate evolution. Importantly, gene structure comparisons and synteny analysis of jawless vertebrate (cyclostome) TCFs suggest that a TCF7L2‐like form of gene structure is a close proxy for the ancestral vertebrate structure. In conclusion, we propose a detailed evolutionary path based on a new pre‐whole‐genome duplication vertebrate TCF gene model. This ancestor gene model highlights the chordate and vertebrate innovations of TCF/LEF gene structure, providing the foundation for understanding the role of Wnt/β‐catenin signaling in vertebrate evolution. The canonical Wnt/β‐catenin signaling pathway acts through the TCF/LEF family of transcription factors. The step change in diversity of the genes in this family across the invertebrate–vertebrate transition is described here, via a new evolutionary model that includes the inferred intermediate genes in this transition. This provides a foundation for future work on the functional diversity of these genes in development and disease.
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