Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle.牛基因组序列为系统性关联牛的遗传与代谢性状提供了宝贵契机。本研究的目标有二：其一，基于最新更新的牛基因组组装版本，重构基因组规模的牛特异性代谢通路；其二，鉴定牛基因组内的重复代谢基因，以深入解析牛的代谢适应性。本研究更新了一款用于整合多源基因组注释信息的生物信息学流程，并基于该流程构建了以UMD_3.1为参考的整合型牛基因组数据库。该整合型牛基因组数据库共包含33292个基因：其中NCBI与Ensembl数据库共有的共识基因为19123个，仅在NCBI或Ensembl中检出的基因分别为8410个与5493个，另有266个基因来源于NCBI基因组支架（scaffolds）。研究还借助Pathway Tools工具构建了牛基因组代谢重构模型与牛通路基因组数据库（Pathway Genome Database, PGDB），并开展了深度人工手动注释校正。本次人工校正共填补或修订了68个通路缺口，删除了36条代谢通路，新增23条代谢通路。经校正后的牛PGDB共包含304条代谢通路、2460个反应（其中2371个为酶促反应）以及4012种酶。此外，相较于人类与小鼠基因组，本研究在牛基因组的12条代谢通路中鉴定出8个重复代谢基因，其中部分基因与特定激素生物合成及解毒过程相关。本次更新的基因组规模代谢重构模型可为解析牛的生物学特性与代谢特征提供有效研究工具。当前牛基因组注释质量与MetaCyc数据库的质量均得到显著提升。相较于人类与小鼠，牛基因组中存在的重复代谢基因暗示了牛基因组的演化改变，同时为后续解析牛代谢适应性的相关研究提供了有价值的参考信息。