ABSTRACT: Purpose: The goal of this study was to perform a transcriptome-wide analysis of variation in brain gene expression between domesticated pig and wild boars using illumina sequencing strategy. Methods: Brain mRNA profiles of wild boars and Rongchang pigs were generated by deep sequencing, in triplicate, using Illumina Hiseq2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Results: We identified 808 widely-expressed conserved and 697 species-specific novel miRNAs in two species. In addition, although two organs showed similar high expression miRNAs, larger differentiation was present in lung than heart between two species. In addition, miRNAs with significantly differentiated patterns of expression in two organs exhibited obvious co-operation effect in high altitude adaptation in form of miRNA family and cluster. Functional analysis revealed that a large amount of differentially expressed miRNAs were enriched in hypoxia-related pathways, such as VEGF signaling pathway, HIF-1α signaling pathway, insulin signaling pathway, DNA damage response, apoptosis, fatty acid metabolism and glucose metabolism. These results suggested the diverse degrees of epigenetic variation in different tissues between yak and cattle, and revealed extensive roles of miRNAs in high altitude adaptation. Conclusions: First, we totally identified 20,805 genes in two groups, of which 18,904 in wild boar and 17,980 in Rongchang pigs, respectively. Second, we detected substantial variation in expression profiles between wild boar and Rongchang pig, including substantial wild boar/Rongchang specifically expressed genes and differentially expressed genes. The functional enrichment analysis revealed immune response was enriched for genes upregulated in wild boars. Finally, we compared our results against previous study and identified seven genes that were associated with domestication.The work performed here will provide a typical demonstration for future deciphering the mechanism of pig domestication.