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Abstract Background Thousands of years of natural and artificial selection since the domestication of the horse has shaped the distinctive genomes of Chinese Mongolian horse populations. Consequently, genomic signatures of selection can provide insights into the human-mediated selection history of specific traits and evolutionary adaptation to diverse environments. Here, we used genome-wide SNPs from five distinct Chinese Mongolian horse populations to identify genomic regions under selection for the population-specific traits, gait, black coat colour, and hoof quality. Other global breeds were used to identify regional-specific signatures of selection. Results We first identified the most significant selection peak for the Wushen horse in the region on ECA23 harbouring DMRT3, the major gene for gait. We detected selection signatures encompassing several genes in the Baicha Iron Hoof horse that represent good biological candidates for hoof health, including the CSPG4, PEAK1, EXPH5, WWP2 and HAS3 genes. In addition, an analysis of regional subgroups (Asian compared to European) identified a single locus on ECA3 containing the ZFPM1 gene that is a marker of selection for the major domestication event leading to the DOM2 horse clade. Conclusions Genomic variation at these loci in the Baicha Iron Hoof may be leveraged in other horse populations to identify animals with superior hoof health or those at risk of hoof-related pathologies. The overlap between the selection signature in Asian horses with the DOM2 selection peak raises questions about the nature of horse domestication events, which may have involved a prehistoric clade other than DOM2 that has not yet been identified.

Abstract Background Bovine TB (bTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production. The key innate immune cell that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection. Results The host gene expression data consisted of RNA-seq data from bovine alveolar macrophages (bAM) infected with M. bovis at 24 and 48 h post-infection (hpi) compared to non-infected control bAM. These RNA-seq data were analysed using three distinct computational pipelines to produce six separate gene sets: 1) DE genes filtered using stringent fold-change and P-value thresholds (DEG-24: 378 genes, DEG-48: 390 genes); 2) genes obtained from expression correlation networks (CON-24: 460 genes, CON-48: 416 genes); and 3) genes obtained from differential expression networks (DEN-24: 339 genes, DEN-48: 495 genes). These six gene sets were integrated with three bTB breed GWAS data sets by employing a new genomics data integration tool—gwinteR. Using GWAS summary statistics, this methodology enabled detection of 36, 102 and 921 prioritised SNPs for Charolais, Limousin and Holstein-Friesian, respectively. Conclusions The results from the three parallel analyses showed that the three computational approaches could identify genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets. These analyses also demonstrated significant differences among breeds, with the Holstein-Friesian breed GWAS proving most useful for prioritising SNPS through data integration. Because the functional genomics data were generated using bAM from this population, this suggests that the genomic architecture of bTB resilience traits may be more breed-specific than previously assumed.

Abstract Background Mastitis in dairy cows caused by Staphylococcus aureus is a major problem hindering economic growth in dairy farms worldwide. It is difficult to prevent or eliminate due to its asymptomatic nature and long persistence of infection. Although transcriptomic responses of bovine mammary gland cells to pathogens that cause mastitis have been studied, the common responses of peripheral blood leukocytes to S. aureus infection across two consecutive generations of dairy cattle have not been investigated. Methods In the current study, RNA-Seq was used to profile the transcriptomes of peripheral blood leukocytes sampled from S. aureus-infected mothers and their S. aureus-infected daughters, and also healthy non-infected mothers and their healthy daughters. Differential gene expression was evaluated as follows: 1) S. aureus-infected cows versus healthy non-infected cows (S vs. H, which include all the mothers and daughters), 2) S. aureus-infected mothers versus healthy non-infected mothers (SM vs. HM), and 3) S. aureus-infected daughters versus healthy non-infected daughters (SMD vs. HMD). Results Analysis of all identified expressed genes in the four groups (SM, SMD, HM, and HMD) showed that EPOR, IL9, IFNL3, CCL26, IL26 were exclusively expressed in both the HM and HMD groups, and that they were significantly (P 1.2) were detected in the three comparisons, respectively. DEGs with P 2 were used for functional enrichment analyses. For the S vs. H comparison, DEGs detected included CCL20, IL13 and MMP3, which are associated with the IL-17 signaling pathway. In the SM vs. HM and SMD vs. HMD comparisons, five (BLA-DQB, C1R, C2, FCGR1A, and KRT10) and six (BLA-DQB, C3AR1, CFI, FCAR, FCGR3A, and LOC10498484) genes, respectively, were involved in the S. aureus infection pathway. Conclusions Our study provides insights into the transcriptomic responses of bovine peripheral blood leukocytes across two generations of cattle naturally infected with S. aureus. The genes highlighted in this study could serve as expression biomarkers for mastitis and may also contain sequence variation that can be used for genetic improvement of dairy cattle for resilience to mastitis.

Abstract Animal domestication has fascinated biologists since Charles Darwin first drew the parallel between evolution via natural selection and human-mediated breeding of livestock and companion animals. In this review we show how studies of ancient DNA from domestic animals and their wild progenitors and congeners have shed new light on the genetic origins of domesticates, and on the process of domestication itself. High-resolution paleogenomic data sets now provide unprecedented opportunities to explore the development of animal agriculture across the world. In addition, functional population genomics studies of domestic and wild animals can deliver comparative information useful for understanding recent human evolution.

Abstract Background A single bout of exercise induces changes in gene expression in skeletal muscle. Regular exercise results in an adaptive response involving changes in muscle architecture and biochemistry, and is an effective way to manage and prevent common human diseases such as obesity, cardiovascular disorders and type II diabetes. However, the biomolecular mechanisms underlying such responses still need to be fully elucidated. Here we performed a transcriptome-wide analysis of skeletal muscle tissue in a large cohort of untrained Thoroughbred horses (n = 51) before and after a bout of high-intensity exercise and again after an extended period of training. We hypothesized that regular high-intensity exercise training primes the transcriptome for the demands of high-intensity exercise. Results An extensive set of genes was observed to be significantly differentially regulated in response to a single bout of high-intensity exercise in the untrained cohort (3241 genes) and following multiple bouts of high-intensity exercise training over a six-month period (3405 genes). Approximately one-third of these genes (1025) and several biological processes related to energy metabolism were common to both the exercise and training responses. We then developed a novel network-based computational analysis pipeline to test the hypothesis that these transcriptional changes also influence the contextual molecular interactome and its dynamics in response to exercise and training. The contextual network analysis identified several important hub genes, including the autophagosomal-related gene GABARAPL1, and dynamic functional modules, including those enriched for mitochondrial respiratory chain complexes I and V, that were differentially regulated and had their putative interactions ‘re-wired’ in the exercise and/or training responses. Conclusion Here we have generated for the first time, a comprehensive set of genes that are differentially expressed in Thoroughbred skeletal muscle in response to both exercise and training. These data indicate that consecutive bouts of high-intensity exercise result in a priming of the skeletal muscle transcriptome for the demands of the next exercise bout. Furthermore, this may also lead to an extensive ‘re-wiring’ of the molecular interactome in both exercise and training and include key genes and functional modules related to autophagy and the mitochondrion.