A high resolution atlas of gene expression in the domestic sheep ( Ovis aries)

Abstract

Sheep are a key source of meat, milk and fibre for the global livestock sector, and an important biomedical model. Global analysis of gene expression across multiple tissues has aided genome annotation and supported functional annotation of mammalian genes. We present a large-scale RNA-Seq dataset representing all the major organ systems from adult sheep and from several juvenile, neonatal and prenatal developmental time points. The Ovis aries reference genome (Oar v3.1) includes 27,504 genes (20,921 protein coding), of which 25,350 (19,921 protein coding) had detectable expression in at least one tissue in the sheep gene expression atlas dataset. Network-based cluster analysis of this dataset grouped genes according to their expression pattern. The principle of ‘guilt by association’ was used to infer the function of uncharacterised genes from their co-expression with genes of known function. We describe the overall transcriptional signatures present in the sheep gene expression atlas and assign those signatures, where possible, to specific cell populations or pathways. The findings are related to innate immunity by focusing on clusters with an immune signature, and to the advantages of cross-breeding by examining the patterns of genes exhibiting the greatest expression differences between purebred and crossbred animals. This high-resolution gene expression atlas for sheep is, to our knowledge, the largest transcriptomic dataset from any livestock species to date. It provides a resource to improve the annotation of the current reference genome for sheep, presenting a model transcriptome for ruminants and insight into gene, cell and tissue function at multiple developmental stages.

Author summary

Sheep are ruminant mammals kept as livestock for the production of meat, milk and wool in agricultural industries across the globe. Genetic and genomic information can be used to improve production traits such as growth rate and health and fitness traits including disease resilience. The sheep genome is, however, missing important information relating to gene function and many genes, which may be important for productivity, have no informative gene name. This can be remedied using RNA-Sequencing to generate a global expression profile of all protein-coding genes, across multiple organ systems and developmental stages. Clustering genes based on their expression profile across tissues and cells allows us to assign function to those genes. If, for example, a gene with no informative gene name is expressed in macrophages and is found within a cluster of known macrophage related genes it is likely to be involved in macrophage function and play a role in innate immunity. This information improves the quality of the reference genome and provides insight into biological processes underlying the complex traits that influence the productivity of sheep and other livestock species.