Table_2_A brief history of galectin evolution.docx

Galectins are a family of carbohydrate-binding proteins found in vertebrates in great abundance and diversity in terms of both structure and ligand-binding properties as well as physiological function. Proteins with clear relationships to vertebrate galectins are already found in primitive Bilateria. The increasing amount of accessible well-annotated bilaterian genomes has allowed us to reveal, through synteny analyses, a new hypothesis about the phylogenetic history of the galectin family in this animal group. Thus, we can trace the genomic localization of the putative ancestral Bilateria galectin back to the scallops as a still very primitive slow-evolving bilaterian lineage. Intriguingly, our analyses show that the primordial galectin of the Deuterostomata most likely exhibited galectin-8-like characteristics. This basal standing galectin is characterized by a tandem-repeat type with two carbohydrate recognition domains as well as by a sialic acid binding property of the N-terminal domain, which is typical for galectin-8. With the help of synteny, the amplification of this potential primordial galectin to the broad galectin cosmos of modern jawed vertebrates can be reconstructed. Therefore, it is possible to distinguish between the paralogs resulting from small-scale duplication and the ohnologues generated by whole-genome duplication. Our findings support a substantially new hypothesis about the origin of the various members of the galectin family in vertebrates. This allows us to reveal new theories on the kinship relationships of the galectins of Gnatostomata. In addition, we focus for the first time on the galectines of the Cyclostomata, which as a sister group of jawed vertebrates providing important insights into the evolutionary history of the entire subphylum. Our studies also highlight a previously neglected member of the galectin family, galectin-related protein 2. This protein appears to be a widespread ohnologue of the original tandem-repeat ancestor within Gnathostomata that has not been the focus of galectin research due to its nonclassical galactose binding sequence motif and the fact that it was lost during mammalian evolution.

半乳糖凝集素是一类在脊椎动物中广泛存在且结构多样、糖基结合特性及生理功能丰富的碳水化合物结合蛋白家族。与脊椎动物半乳糖凝集素有明确关联的蛋白质已在原始两侧对称动物中找到。随着可访问、注释完善的两侧对称动物基因组数量的增加，我们得以通过同源分析揭示该动物群中半乳糖凝集素家族的进化历史的新假说。因此，我们可以追溯假想的原始两侧对称动物半乳糖凝集素的基因组定位，回溯至蚌类这一仍处于非常原始且缓慢进化的两侧对称动物谱系。令人好奇的是，我们的分析表明，原初的脊索动物半乳糖凝集素很可能表现出类似半乳糖凝集素-8的特征。这一基础稳定的半乳糖凝集素以串联重复型、两个碳水化合物识别域以及N端域的神经节苷酸结合特性为特征，后者是半乳糖凝集素-8的典型特征。借助同源分析，我们可以重建这一潜在原始半乳糖凝集素在现生有颌脊椎动物广泛半乳糖凝集素宇宙中的扩增过程。因此，我们能够区分由小规模复制产生的同源物和由全基因组复制产生的类同源物。我们的研究结果支持关于脊椎动物中半乳糖凝集素家族各种成员起源的全新假说。这使我们能够揭示关于Gnatostomata中半乳糖凝集素亲缘关系的新的理论。此外，我们首次关注了圆口类动物的半乳糖凝集素，作为有颌脊椎动物的同源群，它为整个亚门的进化历史提供了重要见解。我们的研究还突出了半乳糖凝集素家族先前被忽视的成员——半乳糖凝集素相关蛋白2。这种蛋白似乎是有颌脊椎动物内广泛存在的原始串联重复祖先的同源物，由于它的非经典半乳糖结合序列模式和它在哺乳动物进化过程中的丢失，它并未成为半乳糖凝集素研究的焦点。