Genetic determinants of genus-level glycan diversity in a bacterial protein glycosylation system
Genetic determinants of genus-level glycan diversity in a bacterial protein glycosylation system
复制标题
DOI：
10.1371/journal.pgen.1008532
复制
发表时间：
2019-12-01
期刊：
影响因子：
4.5
通讯作者：
Koomey, Michael
中科院分区：
文献类型：
--
作者：
Hadjineophytou, Chris;Anonsen, Jan Haug;Koomey, Michael
人类病原体N.淋病奈瑟菌和淋病奈瑟菌。脑膜炎病毒显示出与其O-连接蛋白糖基化（pgl）系统相关的强大的株内和株间聚糖多样性。为了更好地理解蛋白质糖基化的进化和功能，我们的目的是确定其他人类限制的奈瑟氏菌属物种是否类似地糖基化蛋白质，如果是，评估糖型多样性的水平。比较基因组学揭示了O-连接蛋白糖基化聚糖所需的基因的一个子集的保守性，并建立了这些pgl基因作为该属的核心基因组成分。结合基于质谱的聚糖表型分析，我们发现N。gonorrhoeae、淋病奈瑟菌N. meningitidis和近缘种N. polysaccharea和N.内酰胺反映了祖聚糖生物合成途径的功能替代。这种替换涉及原始途径的pgl基因组分的丢失，同时获得两个外源糖基转移酶基因。这一发现的关键是鉴定了一个普遍存在但以前未被识别的糖基转移酶基因（pglP），该基因在N.淋病奈瑟菌和淋病奈瑟菌。脑膜炎我们认为，pseudogenization事件是由过程的成分上位性导致基因衰变。此外，我们记录的情况下，种间重组影响pgl基因的状态，并创建不协调的遗传相互作用，由于表面上的多位点性质的pgl基因网络。总之，这些研究结果提供了一个新的角度对蛋白质糖基化系统的演变，并确定与奈瑟菌属物种相关的遗传信息，遗传差异。
The human pathogens N. gonorrhoeae and N. meningitidis display robust intra- and interstrain glycan diversity associated with their O-linked protein glycosylation (pgl) systems. In an effort to better understand the evolution and function of protein glycosylation operating there, we aimed to determine if other human-restricted, Neisseria species similarly glycosylate proteins and if so, to assess the levels of glycoform diversity. Comparative genomics revealed the conservation of a subset of genes minimally required for O-linked protein glycosylation glycan and established those pgl genes as core genome constituents of the genus. In conjunction with mass spectrometric-based glycan phenotyping, we found that extant glycoform repertoires in N. gonorrhoeae, N. meningitidis and the closely related species N. polysaccharea and N. lactamica reflect the functional replacement of a progenitor glycan biosynthetic pathway. This replacement involved loss of pgl gene components of the primordial pathway coincident with the acquisition of two exogenous glycosyltransferase genes. Critical to this discovery was the identification of a ubiquitous but previously unrecognized glycosyltransferase gene (pglP) that has uniquely undergone parallel but independent pseudogenization in N. gonorrhoeae and N. meningitidis. We suggest that the pseudogenization events are driven by processes of compositional epistasis leading to gene decay. Additionally, we documented instances where interspecies recombination influences pgl gene status and creates discordant genetic interactions due ostensibly to the multi-locus nature of pgl gene networks. In summary, these findings provide a novel perspective on the evolution of protein glycosylation systems and identify phylogenetically informative, genetic differences associated with Neisseria species.