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Background: Tibetan chickens living at high altitudes show specific adaptations to high-altitude conditions, but the epigenetic modification bases of these adaptations haven’t been characterized.

Results: We investigated the genome-wide DNA methylation patterns in Tibetan chicken bloodusing whole genome bisulfite sequencing (WGBS). Generally, Tibetan chicken exhibited analogous methylation pattern with that of lowland chiken. A total of 3.92% of genomic cytosines were methylcytosines, and 51.22% of cytosines in CG contexts were methylated which was less than those in lowland chicken (55.69%). Moreover, the base next to methylcytosine of mCHG in Tibetan chicken had a preference for T, which was different from that in lowland chicken. In Tibetan chicken, the methylation levels in the promoter were relatively low, while the gene body maintained hypomethylated. DNA methylation levels in upstream regions of the transcription start site (TSS) of geneshad a negative relationship with the gene expression level, and the DNA methylation of gene-body were also negatively related to gene expression.

Conclusions: We firstly generated the genome-wide DNA methylation patterns in Tibetan chicken, and our results will be helpful for future epigenetic studies in adaptations to high-altitude conditions and provide a new idea for the prevention and treatment of mountain sickness and other hypoxia-related diseases to human.

Keywords: Epigenetics, DNA methylation, MethylC-Seq, highland chicken, adaptation, extreme environment.



DNA methylation is a crucial epigenetic modification that plays a vital role in genomic imprinting [1], transcriptional repression [2], and chromatin activation [3]. In recent years, we have gained knowledge on the association of DNA methylation with cellular differentiation, development, and disease, however, little information is available concerning the DNA methylation modifications under long-term extreme environment.

Environmental aspects influence through both genetic and epigenetic mechanisms [4, 5]. Several studies have tried to establish the relationship between environmental factors and DNA methylation in humans. It was reported that reduced global DNA methylation in whole blood was related to exposure to ambient air pollution at the home addresses of non adults [6]. In malignant cells, airborne benzene induce a significant decrease in the methylation of LINE-1 and AluI, and increasing airborne benzene levels can cause hypermethylation in p15 and hypomethylation in MAGE-1 [7]. The average level of methylation in p16 was increased in patients with benzene poisoning compared with control group, while no alternation was observed in the p15 methylation [8]. Korea et al. revealed that most organochlorine (OC) pesticides were inversely and significantly related to the methylation of Alu [9]. In the prenatal pregnant women, lead exposure was inversely related to genomic DNA methylation in white blood cells [10]. Moreover, base on the epigenetic inheritance mechanisms, adaptive traits that result from the environment can be transferred to the next generation. For instance, environment containing endocrine-disrupting chemicals can affect the germ line and promote disease across offspring via DNA methylation [11].

Above researchs shows that environmental conditions could induce DNA methylation alternation to to influence disease, prompting us to explore whether DNA methylation is associated with the unique adaptations of farm animals to hypoxia and high-dose ultraviolet radiation in high-altitude environments. The Tibetan chicken which lives in high-altitude environment has smaller body, lower heart rate, higher spleen rate and erythrocyte volum than low-altitude chicken. Previous research showed that humans relocating to high-altitudes might undergo acute mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema [12]. Whereas, the Tibetan chicken is greatly adapted to the low-oxygen and high-altitude environment and displays good performance in terms of survival and has high reproduction [13]. Therefore, investigation the genome-wide DNA methylation of Tibetan chicken, understanding the effects of DNA methylation on the plateau adaptability, may provide a new idea for the prevention and treatment of mountain sickness and other hypoxia-related diseases to human.

In this study, we perform whole genome bisulfite sequencing (WGBS) on Tibetan chicken blood to analyze their global DNA methylation patterns. The DNA methylome distribution in the Tibetan chicken genome was shown for the first time. Our results will provided an important resource for exploring low-oxygen adaptation mechanism in high-altitude district.