基于比较基因组学对新疆不同地域人源长双歧杆菌长亚种的遗传差异分析

Comparative genomics reveals the genetic differences of human-derived Bifidobacterium longum subsp. longum in different regions of Xinjiang

摘要:

目的 以新疆不同地域、不同人群来源的长双歧杆菌长亚种(Bifidobacterium longum subsp. longum)为研究对象，解析肠道专性共栖细菌在宿主人群中的系统发育和基因组多样性，为针对不同人群开发个性化功能益生菌提供理论依据。方法 从地理跨度较大的新疆喀什、伊犁的维吾尔族和哈萨克族母婴人群中分离出136株B. longum subsp. longum，并通过公共数据库整合来自国内其他地域人群的菌株进行比较基因组分析。结果 B. longum subsp. longum基因组的平均大小、G+C含量、编码序列数量分别为2.38 Mb、59.91%、2 160个。基于核心基因构建的系统发育树显示，来自新疆的所有菌株在系统发育树上属于4个进化支(clade)，来自同一民族、不同地域人群的菌株其系统发育呈现不同的进化支，地理上更相近、不同人群来源的菌株存在一定程度的重叠。对更大地理范围(全中国)的分析显示，B. longum subsp. longum菌株呈现明显的东西部地理来源聚集特征和协同进化现象。基于附属基因和碳水化合物代谢功能基因的分析显示，来源于同一系统发育进化支的同一民族、不同地域人群菌株的功能基因谱丰度也差异较大；碳水化合物水解酶家族GH13 (α-淀粉酶)和GH43 (β-木糖苷酶)等在喀什地区菌株基因组中更为丰富；相反，地理上相近、即使来自不同民族人群的菌株，其基因组中蛋白质直系同源簇(cluster of orthologous groups of proteins, COG)功能基因谱、碳水化合物水解酶关联基因家族谱更相似。结论 新疆不同地域人群来源的B. longum subsp. longum菌株系统发育呈现明显的地理和民族分布特征以及功能基因分布特征，地理尺度范围越大，菌株的地理分布特征越明显。需要基于更大范围菌株基因组的大数据进一步验证人群的地理分布尺度与菌株协同进化和特异性的关系。

Abstract:

Objective To study the phylogenetic relationship and genomic diversity of intestinal obligate commensal bacteria in different populations from various regions of Xinjiang and provide a theoretical basis for developing personalized functional probiotics for different populations.Methods A total of 136 strains of Bifidobacterium longum subsp. longum were isolated from mother-infant populations of Uygur and Kazak ethnic groups in Kashgar and Yili regions of Xinjiang. Comparative genomic analysis was conducted with data of the strains from other regions in China that were available in public databases.Results The average genome size, G+C content, and the number of coding sequences of B. longum subsp. longum were 2.38 Mb, 59.91%, and 2 160, respectively. The phylogenetic tree constructed based on core genes showed that all strains from Xinjiang belonged to four clades in the phylogenetic tree. Strains from the same ethnic group but from different geographical regions were in different clades, and there was a certain degree of overlap between geographically closer and different population-derived strains. The analysis of a larger geographical range (China) showed that B. longum subsp. longum strains and their functional genes presented obvious geographical and ethnic distribution characteristics. The analysis of COG functional genes and carbohydrate hydrolyase-related genes showed that the functional gene spectra varied greatly among strains from the same ethnic group but in different regions. The carbohydrate hydrolyase-related gene families GH13 (α-amylases) and GH43 (β-amylases) were more abundant in the strains from Kashgar region. Conversely, even strains from different ethnic groups but from geographically close regions had similar spectra of COG functional genes and carbohydrate hydrolyase-related gene families.Conclusion The B. longum subsp. longum strains and their functional genes from different geographical regions and ethnic groups in Xinjiang showed obvious geographical and ethnic distribution characteristics. As the geographical scale becomes large, the geographical distribution characteristics of the strains become more obvious. The relationship between the geographical distribution scale of populations and the co-evolution and specificity of strains should be verified based on larger-scale genomic data of strains.