A Pig BodyMap Transcriptome Reveals Diverse Tissue Physiologies and Evolutionary Dynamics of Transcription [non-human Hi-C]

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）开展的全面转录组学研究，有助于深入解析支撑该物种经济性状的组织特化分子机制，并加速其作为生物医学模型的应用进程。本研究对31个成年猪组织及2种细胞系中的4类不同转录本类型——长链非编码RNA（lncRNAs）、未知编码潜能转录本（TUCPs）、微RNA（miRNAs）及环状RNA（circRNAs），连同蛋白质编码基因，进行了特征注释。我们解析了各类转录本独特的结构与转录特征，并揭示了与组织生理功能相关的转录组变异规律。研究发现，47种解剖学特征各异的骨骼肌及6处脂肪库之间存在显著的转录组多样性，这种多样性与其不同的起源、代谢特征、细胞组成、运动状态及线粒体通路密切相关。尤为值得注意的是，骨骼肌中HOX基因的转录呈现位置依赖性模式，揭示了同一躯体部位内这些组织具有相似的发育起源。不同脂肪库的转录模式表明，皮下脂肪组织具有代谢保护功能，而内脏脂肪组织则与代谢功能异常存在关联。通过对家猪7种组织与另外9种脊椎动物对应组织的转录组进行比较分析，我们解析了转录演化分化的规律，该规律有助于理解物种特异性的组织生物学特性。我们还针对6种哺乳动物的皮下脂肪组织，分析了增强子通过远程调控启动子并影响下游转录的机制，结果表明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，从而在物种形成过程中赋予表达鲁棒性。综上，本研究为推动家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的数据资源，同时也揭示了其多样经济性状的分子基础。