Population genetic variations of the MMP3 gene revealed hypoxia adaptation in domesticated yaks (Bos grunniens).

Xuezhi Ding,Xian Guo,Jie Pei,Xiaoyun Wu,Pengjia Bao,Ping Yan,Chao Yang

doi:10.5713/ajas.17.0706

Abstract

ObjectiveAs an iconic symbol of Qinghai-Tibetan Plateau and of high altitude, yak are subjected to hypoxic conditions that challenge aerobic metabolism. Matrix metalloproteinases-3 (MMP3) is assumed to be a key target gene of hypoxia-inducible factor-1α that function as a master regulator of the cellular response to hypoxia. Therefore, the aim of this investigation was to identify the DNA polymorphism of MMP3 gene in domestic yak and to explore its possible association with high-altitude adaptation.MethodsThe single-nucleotide polymorphisms (SNPs) genotyping and mutations scanning at the MMP3 locus were conducted in total of 344 individuals from four domestic Chinese yak breeds resident at different altitudes on the Qinghai-Tibetan Plateau, using high-resolution melting analysis and DNA sequencing techniques.ResultsThe novel of SNPs rs2381 A→G and rs4331 C→G were identified in intron V and intron VII of MMP3, respectively. Frequencies of the GG genotype and the G allele of SNP rs2381 A→G observed in high-altitude Pali yak were significantly higher than that of the other yak breeds resident at middle or low altitude (p<0.01). No significant difference was mapped for SNP rs4331 C→G in the yak population (p>0.05). Haplotype GC was the dominant among the 4 yak breeds, and Pearson correlation analysis showed that the frequencies of GC was significantly lower in Ganan (GN), Datong (DT), and Tianzhu white yaks (TZ) compared with Pali (PL) yak. The two SNPs were in moderate linkage disequilibrium in high-altitude yaks (PL) but not in middle-altitude (GN, DT) and low-altitude (TZ) yaks.ConclusionThese results indicate that MMP3 may have been subjected to positive selection in yak, especially that the SNP rs2381 A→G mutation and GC haplotypes might contribute to adaptation for yak in high-altitude environments.

Highlights

Hypoxia is one of the most important factors affecting survival in high-altitude regions
PL, DT, Tianzhu white yaks (TZ) of rs2381 A→G were in Hardy-Weinberg equilibrium (HWE) (p>0.05), while GN yaks of rs2381 A→G were in HWE (p
Three genotypes (CC, CG, GG; Figure 1B) were sel ected for the single-nucleotide polymorphisms (SNPs) rs4331 C→G, CC genotype and C allele were the dominant among the four yak breeds

Summary

Introduction

Hypoxia is one of the most important factors affecting survival in high-altitude regions. Several candidate genes were associated with high-altitude hypoxia in Tibetan sheep [9]. Almost all of the identified genes which belong to the list of 247 hypoxia genes that are priority candidates for adaptation to high-altitude hypoxia [12]; Our recent studies have demonstrated that the positively selected haplotypes of EPAS1 was significantly asso ciated with higher hemoglobin concentration for hypoxia adaptation of yak [13]. Hypoxia-inducible factors (HIFs) are transcription factors that respond to changes in the available oxygen in the cellular environment under high-altitude con ditions. The ADAM17 and ARG12 proteins affect HIF-1α stability and activity by regulating production of tumor necrosis factor α (TNF-α) and nitric oxide, respectively [23,24], whereas MMP3 has key roles in numerous physiological processes [25]. The aim was to identify the polymor phisms of MMP3 in 4 yak breeds from different altitude and local cattle as a comparison to evaluate its association with

Methods

Results

Conclusion