A Pig BodyMap Transcriptome Reveals Diverse Tissue Physiologies and Evolutionary Dynamics of Transcription [RNA-Seq for pig and rat]

Comprehensive transcriptomic survey of the pig (Sus scrofa) may lead to a better understanding of mechanisms of tissue specialization that underlie economic traits of this species and accelerate its use as a biomedical model. Here, we characterized four distinct transcript types (lncRNAs, TUCPs, miRNAs and circRNAs) in 31 adult pig tissues and two cell lines, together with protein-coding genes. We dissected their distinct structural and transcriptional features and uncovered transcriptome variability as related to tissue physiology. We discovered extraordinary diversity among 47 anatomically distinct skeletal muscle types, as well as among six adipose depots, which are linked to their diverse origins, metabolic features, cell composition, physical activity and mitochondrial pathways. In particular, transcription of HOX genes across skeletal muscles exhibited a position-dominant pattern, revealing a similar developmental history of these tissues within the same body part. Transcriptional patterns across adipose depots demonstrated a metabolically protective role of subcutaneous adipose tissue and the association of visceral adipose tissue with metabolic dysfunction. Comparative analysis of the transcriptomes of seven tissues of the pig and nine other vertebrates revealed insights into evolutionary divergence of transcription that contributes to lineage-specific tissue biology. We also analyzed long-range regulation of promoters by their enhancers with downstream transcription in subcutaneous adipose tissues of six mammals, showing that evolutionary stability of transcription can mainly be attributed to multiple enhancers buffering gene expression patterns against genetic perturbations, thereby conferring robustness during speciation. Collectively, this study offers a resource for the accelerated use of the pig as a biomedical model for human biology and disease and uncovers molecular bases of its diverse economic traits.针对家猪（Sus scrofa）的全面转录组全景分析，有助于更深入理解该物种经济性状背后的组织特化机制，并推动其作为生物医学模型的应用。本研究对31种成年猪组织与两种细胞系中的四类转录本——长链非编码RNA（long non-coding RNAs, lncRNAs）、编码潜能未知转录本（transcripts of uncertain coding potential, TUCPs）、微小RNA（microRNAs, miRNAs）及环状RNA（circular RNAs, circRNAs）——与蛋白编码基因进行了系统表征。研究解析了这些转录本独特的结构与转录特征，揭示了与组织生理相关的转录组变异。我们发现，47种解剖学特征各异的骨骼肌类型以及6种脂肪垫之间存在显著的转录组多样性，这一多样性与其多样的起源、代谢特性、细胞组成、运动活性及线粒体通路密切相关。尤为值得关注的是，同源盒基因（homeobox genes, HOX）在骨骼肌中的转录呈现出位置依赖性表达模式，揭示了同一躯体部位内各骨骼肌组织具有相似的发育历程。脂肪垫的转录模式则证实了皮下脂肪组织的代谢保护作用，以及内脏脂肪组织与代谢功能障碍的关联。通过对猪的7种组织与其他9种脊椎动物的转录组开展比较分析，本研究揭示了转录进化分化的相关机制，该机制促成了谱系特异性的组织生物学特征。此外，我们以六种哺乳动物的皮下脂肪组织为研究对象，分析了增强子对启动子的远程调控及其下游转录过程，发现转录的进化稳定性主要源于多个增强子可缓冲基因表达模式以抵御遗传扰动，进而在物种形成过程中赋予表达鲁棒性。综上，本研究为加速将猪作为人类生物学与疾病研究的生物医学模型提供了宝贵资源，同时阐明了其多样经济性状的分子基础。