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Background  The domestic pig  Sus scrofa domesticus  originated from the wild boar  S. scrofa  about 10,000 years ago. During domestication, drastic morphological, physiological, and behavioral changes developed between domestic pigs and wild boars through artificial and natural selection. The long non-coding RNA (lncRNA)  H19 , which is located within the imprinting gene cluster  H19-IGF2 , plays an important role in regulating muscle development in humans and mice. This study systematically analyzed the molecular evolution of  H19  and its possible epigenetic changes during pig domestication and breeding to explore the genetic and epigenetic contributions of  H19  to pig domestication.    Results  The molecular evolution of  H19  was initially analyzed on a large phylogenetic scale. Results showed that the gene was highly conserved within a broad range, especially in the 5′ terminal sequence. The molecular evolution of the gene was then analyzed using published re-sequencing data of 30 wild boars from Tibet, 3 wild boars from Sichuan, and 15 native pigs from other regions in China. Eight polymorphic sites were identified, and the nucleotide diversity (π) value within the  H19  gene body was significantly higher (Z-test,  P  < 0.05) in domesticated pigs than in wild pigs. However, no significant divergence occurred between domesticated and wild pigs. Single nucleotide polymorphisms in the 3′ terminal sequence were surveyed in other Chinese local breeds and foreign pig breeds. We observed a consistently higher diversity in domesticated pigs than in wild pigs. The methylation pattern of the  H19  gene in pigs was subsequently analyzed using published methylated DNA immunoprecipitation data and an unpublished single-base resolution liver methylome. Analysis results showed distinct methylation levels in some tissues. Among the samples surveyed, Landrace showed the lowest methylation level, followed by the Guizhou wild boar, whereas the Enshi pig exhibited the highest methylation level in the 2 kb upstream region of the  H19  gene. Liver transcriptome data suggested that Landrace harbored the highest expression of the  H19  gene, followed by the Guizhou wild boar, whereas the Enshi pig harbored the lowest expression of the gene. Differential methylation sites (DMSs) among the three breeds were mainly identified in the 2 kb upstream region of the  H19  gene. In the Enshi pig, we detected allele-specific methylation (ASM) regions in the 2 kb upstream region of the  H19  gene. Most of the DMSs in the upstream 2 kb region of the gene were also located in the ASM region in this breed.    Conclusions  Molecular analyses suggest that the  H19  gene was highly conserved during large-scale evolution and exhibited genotype differentiation during domestication and breed differentiation. The drastic diversity pattern between domestic and wild pigs in the  H19  gene body, which was highly conserved during large-scale evolution, suggests that this gene might have played roles in the breed differentiation of domestic pigs. Methylation analysis indicates an opposite epigenetic regulation direction between Chinese and European pig (EU) domestication, which resulted in opposite expression changes in this gene between the two domesticated groups. Our preliminary analyses on DMSs among different pig breeds and ASM imply that imprinting was associated with methylation differences. This study systematically demonstrates the genetic and epigenetic patterns of  H19  during pig domestication and provide valuable cues and basis for further research on the function of  H19  in pig domestication.    Electronic supplementary material  The online version of this article (doi:10.1186/s12862-016-0657-5) contains supplementary material, which is available to authorized users.

Molecular microevolution and epigenetic patterns of the long non-coding gene H19 show its potential function in pig domestication and breed divergence