The distribution of four missense mutations in SPTBN5 gene across native Chinese breeds

Modern cattle belong to two subspecies, Bos taurus and Bos indicus. Since divergence, cattle types have accumulated different genetic variations, which have contributed to highly differentiated phenotypes. The mammalian inner ear possesses functional and morphological innovations that contribute to its unique hearing capacities. The spectrin beta, non-erythrocytic 5 (SPTBN5) gene has been shown to play an important function in the inner ear. Four missense mutations: rs522333459 (c.7232G > C:p.Cys2411Ser), rs718838405 (c.6568A > C:p.Met2190Leu), rs516536785 (c.6283C > T:p.Leu2095Phe) and rs480278206 (c.4201T > C:p.Cys1401Arg) were identified in the bovine SPTBN5 gene by whole genome resequencing (http://animal.nwsuaf.edu.cn/code/index.php/BosVar), which might be candidate mutations related with hearing of both taurine and indicine cattle. In our study, PCR and DNA sequencing were used to explore the allele frequencies of four mutations of 971 individuals belonging to 38 native Chinese cattle breeds. We find that four mutant alleles showing strong geographic distribution, consisting with the ancestry distribution of taurine and indicine in China. In addition, we identified four mutations of SPTBN5 were diverged in taurine and indicine cattle showing signatures of adaptive evolution in two subspecies, which might participate in bovine inner ear development.现代家牛可分为两个亚种：普通牛（Bos taurus）与瘤牛（Bos indicus）。自两个亚种分化后，各类家牛均积累了各异的遗传变异，进而造就了高度分化的表型。哺乳动物内耳具备独特的功能与形态创新，这赋予了其独特的听觉能力。血影蛋白β非红细胞5（spectrin beta, non-erythrocytic 5, SPTBN5）基因已被证实在内耳中发挥重要功能。本研究通过全基因组重测序（whole genome resequencing），并借助http://animal.nwsuaf.edu.cn/code/index.php/BosVar数据库，在牛SPTBN5基因中鉴定出4个错义突变：rs522333459 (c.7232G>C:p.Cys2411Ser)、rs718838405 (c.6568A>C:p.Met2190Leu)、rs516536785 (c.6283C>T:p.Leu2095Phe)与rs480278206 (c.4201T>C:p.Cys1401Arg)，上述突变或可作为普通牛与瘤牛听觉相关的候选突变。本研究采用聚合酶链式反应（Polymerase Chain Reaction，PCR）与DNA测序技术，对中国38个本土牛品种的971头个体的4个突变位点的等位基因频率进行了分析。结果显示，4个突变等位基因呈现出显著的地理分布特征，与中国境内普通牛与瘤牛的血统分布高度吻合。此外，本研究发现SPTBN5基因的4个突变在普通牛与瘤牛中发生了分化，呈现出两个亚种的适应性进化信号，推测其可能参与牛内耳的发育过程。