Animal gastrointestinal tracts contain diverse metabolites, including various host-derived compounds that gut-associated microbes interact with. Here, we explore the diversity and evolution of bilirubin reductase, a bacterial enzyme that metabolizes the host-derived tetrapyrrole bilirubin, performing a key role in the animal heme degradation pathway. Through an analysis of the bilirubin reductase phylogeny and predicted structures, we found that the enzyme family can be divided into three distinct clades with different structural features. Using these clade definitions, we analyzed metagenomic sequencing data from multiple animal species, finding that bilirubin reductase is significantly enriched in the large intestines of animals and that the clades exhibit differences in distribution among animals. Combined with phylogenetic signal analysis, we find that the bilirubin reductase clades exhibit significant associations with specific animals and animal physiological traits like gastrointestinal anatomy and diet. These patterns demonstrate that bilirubin reductase is specifically adapted to the anoxic lower gut environment of animals and that its evolutionary history is complex, involving adaptation to a diverse collection of animals harboring bilirubin-reducing microbes. The findings suggest that bilirubin reductase evolution has been shaped by the host environment, providing a new perspective on heme metabolism in animals and highlighting the importance of the microbiome in animal physiology and evolution.

中文翻译：

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胆红素还原酶在动物大肠中显示出宿主特异性关联


动物胃肠道含有多种代谢物，包括与肠道相关微生物相互作用的各种宿主衍生化合物。在这里，我们探讨了胆红素还原酶的多样性和进化，胆红素还原酶是一种代谢宿主衍生的四吡咯胆红素的细菌酶，在动物血红素降解途径中起关键作用。通过对胆红素还原酶系统发育和预测结构的分析，我们发现该酶家族可以分为三个具有不同结构特征的不同分支。使用这些进化枝定义，我们分析了来自多个动物物种的宏基因组测序数据，发现胆红素还原酶在动物的大肠中显着富集，并且进化枝在动物之间表现出分布差异。结合系统发育信号分析，我们发现胆红素还原酶分支与特定动物和动物生理特征（如胃肠道解剖学和饮食）表现出显着关联。这些模式表明胆红素还原酶特别适应动物的缺氧下肠道环境，并且其进化历史很复杂，涉及适应携带胆红素还原微生物的多种动物。研究结果表明，胆红素还原酶的进化受到宿主环境的影响，为动物的血红素代谢提供了新的视角，并强调了微生物组在动物生理学和进化中的重要性。