Lewis Amanda L, Desa Nolan, Hansen Elizabeth E, Knirel Yuriy A, Gordon Jeffrey I, Gagneux Pascal, Nizet Victor, Varki Ajit
Glycobiology Research and Training Center, Departments of Pediatrics, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13552-7. doi: 10.1073/pnas.0902431106. Epub 2009 Jul 28.
Sialic acids (Sias) are nonulosonic acid (NulO) sugars prominently displayed on vertebrate cells and occasionally mimicked by bacterial pathogens using homologous biosynthetic pathways. It has been suggested that Sias were an animal innovation and later emerged in pathogens by convergent evolution or horizontal gene transfer. To better illuminate the evolutionary processes underlying the phenomenon of Sia molecular mimicry, we performed phylogenomic analyses of biosynthetic pathways for Sias and related higher sugars derived from 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids. Examination of approximately 1,000 sequenced microbial genomes indicated that such biosynthetic pathways are far more widely distributed than previously realized. Phylogenetic analysis, validated by targeted biochemistry, was used to predict NulO types (i.e., neuraminic, legionaminic, or pseudaminic acids) expressed by various organisms. This approach uncovered previously unreported occurrences of Sia pathways in pathogenic and symbiotic bacteria and identified at least one instance in which a human archaeal symbiont tentatively reported to express Sias in fact expressed the related pseudaminic acid structure. Evaluation of targeted phylogenies and protein domain organization revealed that the "unique" Sia biosynthetic pathway of animals was instead a much more ancient innovation. Pathway phylogenies suggest that bacterial pathogens may have acquired Sia expression via adaptation of pathways for legionaminic acid biosynthesis, one of at least 3 evolutionary paths for de novo Sia synthesis. Together, these data indicate that some of the long-standing paradigms in Sia biology should be reconsidered in a wider evolutionary context of the extended family of NulO sugars.
唾液酸（Sias）是一类非ulosonic酸（NulO）糖类，在脊椎动物细胞上显著表达，偶尔也会被细菌病原体通过同源生物合成途径模拟。有人提出，唾液酸是动物的一项创新，后来通过趋同进化或水平基因转移出现在病原体中。为了更好地阐明唾液酸分子模拟现象背后的进化过程，我们对唾液酸以及源自5,7-二氨基-3,5,7,9-四脱氧壬-2-ulosonic酸的相关高级糖类的生物合成途径进行了系统发育基因组学分析。对大约1000个已测序的微生物基因组的研究表明，此类生物合成途径的分布比之前认为的要广泛得多。通过靶向生物化学验证的系统发育分析被用于预测各种生物体表达的NulO类型（即神经氨酸、军团氨酸或假氨基糖酸）。这种方法揭示了致病性和共生细菌中唾液酸途径以前未被报道的出现情况，并确定了至少一个实例，即一个曾被初步报道表达唾液酸的人类古菌共生体实际上表达的是相关的假氨基糖酸结构。对靶向系统发育和蛋白质结构域组织的评估表明，动物的“独特”唾液酸生物合成途径实际上是一项更为古老的创新。途径系统发育表明，细菌病原体可能通过适应军团氨酸生物合成途径获得了唾液酸表达，这是从头合成唾液酸的至少3条进化途径之一。总之，这些数据表明，在NulO糖类大家族更广泛的进化背景下，唾液酸生物学中的一些长期范式应该重新考虑。
