Metabolome genome-wide association analyses identify a splice mutation in AADAT affects lysine degradation in duck...

Metabolites in skeletal muscles play an important role in their growth, development, immunity and other physiological activities. However, the genetic basis of metabolites in skeletal muscle remains poorly understood. Here, we identified 247 candidate divergent regions containing 905 protein-coding genes closely related to metabolic pathways, including lysine degradation and fatty acid biosynthesis. We then profiled 3,060 metabolites in 246 skeletal muscle samples from F₂ segregating population generated by mallard×Pekin duck crosses using metabolomic approaches. We identified 2,044 significant metabolome-based GWAS signals and 21 candidate genes potentially modulating metabolite contents in skeletal muscle. Among them, the levels of 2-aminoadipic acid in skeletal muscle were significantly correlated with body weight and intramuscular fat content, determined by a 939-bp CR1 LINE insertion in AADAT. We further found that the CR1 LINE insertion most possibly led to a splice mutation in AADAT, resulting in the downregulation of the lysine degradation pathway in skeletal muscle. Moreover, intramuscular fat content and fatty acids biosynthesis pathway was significantly increased in individuals with CR1 LINE insertion. This study enhances our understanding of the genetic basis of skeletal muscle metabolic traits and promotes the efficient utilization of metabolite traits in the genetic improvement of animals.