Genome methylation and regulatory functions for hypoxic adaptation in Tibetan chicken embryos.

Yawen Zhang,Hongliang Zhang,Wenyu Gou,Ying Zhang,Hao Zhang,Jun Ma

doi:10.7717/peerj.3891

Abstract

Tibetan chickens have unique adaptations to the extreme high-altitude environment that they inhabit. Epigenetic DNA methylation affects many biological processes, including hypoxic adaptation; however, the regulatory genes for DNA methylation in hypoxic adaptation remain unknown. In this study, methylated DNA immunoprecipitation with high-throughput sequencing (MeDIP-seq) was used to provide an atlas of the DNA methylomes of the heart tissue of hypoxic highland Tibetan and lowland Chahua chicken embryos. A total of 31.2 gigabases of sequence data were generated from six MeDIP-seq libraries. We identified 1,049 differentially methylated regions (DMRs) and 695 related differentially methylated genes (DMGs) between the two chicken breeds. The DMGs are involved in vascular smooth muscle contraction, VEGF signaling pathway, calcium signaling pathway, and other hypoxia-related pathways. Five candidate genes that had low methylation (EDNRA, EDNRB2, BMPR1B, BMPRII, and ITGA2) might play key regulatory roles in the adaptation to hypoxia in Tibetan chicken embryos. Our study provides significant explanations for the functions of genes and their epigenetic regulation for hypoxic adaptation in Tibetan chickens.

Highlights

The molecular mechanisms underlying hypoxic adaptation in highland animals have long garnered attention for biological and medical research, because of the evolutionary significance of high-altitude adaptation and in the context of understanding hypoxia in relation to human diseases
The distribution of MeDIP-seq reads in the different genome elements showed that the reads were distributed among all the genomic feature regions (Fig. S3)
The distribution of the MeDIP-seq reads in the CpG islands (CGIs) and its adjacent regions showed a higher level of DNA methylation than the regions 2 kb upstream and downstream of the CGIs (Fig. 1A)

Summary

Introduction

The molecular mechanisms underlying hypoxic adaptation in highland animals have long garnered attention for biological and medical research, because of the evolutionary significance of high-altitude adaptation and in the context of understanding hypoxia in relation to human diseases. Adaptation to hypoxia in animals is a complex trait that involves multigenes and multi-channel regulatory mechanisms. Many indigenous animals, such as the Tibetan antelope (Ge et al, 2013), ground tit (Cai et al, 2013; Qu et al, 2013), yak (Qiu et al, 2012), pig (Li et al, 2013), dog (Gou et al, 2014; Wang et al, 2014), snub-nosed monkey (Yu et al, 2016), and fish (Wang et al, 2015b), have been studied to identify selective signatures and functional genes for adaptation to high altitudes. The increased hatchability of the Tibetan chicken compared with lowland breeds under hypoxia, How to cite this article Zhang et al (2017), Genome methylation and regulatory functions for hypoxic adaptation in Tibetan chicken embryos. The regulatory mechanisms of these hypoxic adaptive genes remain unclear

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