A Novel SNP in EIF2AK4 Gene Is Associated with Thermal Tolerance Traits in Chinese Cattle

SIMPLE SUMMARY: China harbors two lineages of cattle (Bos taurus and Bos indicus) that display pronounced geographical distribution differences. Northern Chinese cattle predominantly belong to B. taurus and southern Chinese cattle belong to B. indicus. Both B. taurus and B. indicus contribute to the admixture of cattle in central China. Thermal stress induces oxidative stress and DNA damage in mammals. In general, B. indicus are more resistant to thermal stress than B. taurus. Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4), which pertains to the family of serine–threonine kinase, is a candidate gene for thermal stress. However, the effects of the bovine EIF2AK4 gene on the thermal tolerance traits of Chinese cattle breeds remain unknown. Our results suggest that a variant of the EIF2AK4 gene is associated with thermal tolerance traits in Chinese cattle. ABSTRACT: Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4, also known as GCN2), which pertains to the family of serine–threonine kinase, is involved in oxidative stress and DNA damage repair. A missense single-nucleotide polymorphism (SNP) (NC_037337.1 g.35615224 T > G) in exon 6 of the EIF2AK4 gene which encodes a p.Ile205Ser substitution was observed in the Bovine Genome Variation Database and Selective Signatures (BGVD). The purpose of the current study is to determine the allelic frequency distribution of the locus and analyze its association with thermal tolerance in Chinese indigenous cattle. In our study, the allelic frequency distribution of the missense mutation (NC_037337.1 g.35615224 T > G) in Chinese cattle was analyzed by sequencing 1105 individuals of 37 breeds including 35 Chinese indigenous cattle breeds and two exotic breeds. In particular, association analysis was carried out between the genotypes and three environmental parameters including annual mean temperature (T), relative humidity (RH), and temperature–humidity index (THI). The frequency of the mutant allele G (NC_037337.1 g.35615224 T > G) gradually decreased from the southern cattle groups to the northern cattle groups, whereas the frequency of the wild-type allele T showed an opposite pattern, consistent with the distribution of indicine and taurine cattle in China. In accordance with the association analysis, genotypes were significantly associated with T (P < 0.01), RH (P < 0.01), and THI (P < 0.01), suggesting that the cattle with genotype GG were found in regions with higher T, RH, and THI. Thus, our results suggest that the mutation (NC_037337.1 g.35615224 T > G) of the EIF2AK4 gene is associated with thermal tolerance traits in Chinese cattle.