基于比较基因组学分析嗜热链球菌的遗传多样性和防御系统

Comparative genomics of genetic diversity and defense system in Streptococcus thermophilus

摘要:

[目的]嗜热链球菌（Streptococcus thermophilus）是发酵乳制品的基础发酵菌种之一，全基因组水平解析嗜热链球菌的遗传多样性和工业发酵特性对于优良发酵菌株的筛选意义重大。[方法]本研究通过比较基因组学方法对27株嗜热链球菌的遗传多样性和防御系统进行分析。[结果]全基因组分析结果显示嗜热链球菌群体内具有较高的遗传多样性；基于核心基因集构建的系统发育树划分为2个分支，其中分支2菌株缺乏完整的组氨酸合成途径，经验证，分支2菌株在缺乏组氨酸的培养基中不能正常生长。通过对嗜热链球菌不同菌株的防御系统进行分析发现，同类型的CRISPR基因座和限制修饰系统在基因组中出现的位置相对固定。CRISPR-Cas系统（P<0.05，r=0.43）和限制修饰系统（P<0.01，r=-0.59）的数量与编码转座酶基因的数量均显著相关，表明嗜热链球菌为了阻止外源DNA入侵会进化出多种防御系统来保护自身遗传完整性。此外，分支1菌株的CRISPR-Cas系统数量极显著（P<0.001）多于分支2，而限制修饰系统无显著差异，表明分支1菌株在噬菌体抗性方面可能更具优势。[结论]本研究基于核心基因构建的系统发育分析将27株嗜热链球菌分为2个分支，不同分支菌株在组氨酸代谢能力和防御系统方面有一定差异。该研究结果为今后快速筛选优良嗜热链球菌发酵剂提供了新思路。

Abstract:

[Objective] Streptococcus thermophilus is one of the most commonly used strains in fermented dairy industry. Therefore, it is important to screen S. thermophilus with good fermentation properties. [Methods] The genetic diversity and defense systems of 27 S. thermophilus genomes were analyzed using comparative genomics. [Results] The genetic diversity of S. thermophilus was high based on whole genome analysis. The phylogenetic tree built based on the core genes was divided into two clades, and the strains in Clade 2 were lack of the complete histidine synthesis pathway, thus could not grow normally in the medium lacking histidine. The analysis of defense systems of S. thermophilus reveals the same type of CRISPR locus and restriction modification system was fixed in the genome relatively. The numbers of CRISPR-Cas (P<0.05, r=0.43) and restriction modification systems (P<0.01, r=-0.59) correlated significantly with the number of genes encoding transposases, indicating S. thermophilus has evolved multiple defense systems to protect its genetic integrity by preventing the invasion of exogenous DNA. In addition, the number of CRISPR-Cas system of the Clade 1 strains was significantly (P<0.001) higher than the Clade 2 strains, whereas there was no significant difference in restriction modification systems. These results suggest that the Clade 1 strains had stronger capacity in resistance to phages. [Conclusion] The phylogenetic analysis based on the core genes was divided into two clades. There were some differences in histidine metabolism and defense system between the different clades, providing a new method for the rapid screening of S. thermophilus starters with excellent fermentation characteristics.