analysis of ultra low genome conservation in clostridium difficile超低梭状芽胞杆菌基因组保护的分析.pdfVIP

Analysis of Ultra Low Genome Conservation in Clostridium difficile 1 2 1,3 1 4 1 Joy Scaria , Lalit Ponnala , Tavan Janvilisri , Weiwei Yan , Lukas A. Mueller , Yung-Fu Chang * 1 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America, 2 Center for Advanced Computing, Cornell University, Ithaca, New York, United States of America, 3 Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand, 4 Boyce Thompson Institute for Plant Research, Ithaca, New York, United States of America Abstract Microarray-based comparative genome hybridisations (CGH) and genome sequencing of Clostridium difficile isolates have shown that the genomes of this species are highly variable. To further characterize their genome variation, we employed integration of data from CGH, genome sequencing and putative cellular pathways. Transcontinental strain comparison using CGH data confirmed the emergence of a human-specific hypervirulent cluster. However, there was no correlation between total toxin production and hypervirulent phenotype, indicating the possibility of involvement of additional factors towards hypervirulence. Calculation of C. difficile core and pan genome size using CGH and sequence data estimated that the core genome is composed of 947 to 1,033 genes and a pan genome comprised of 9,640 genes. The reconstruction, annotation and analysis of cellular pathways revealed highly conserved pathways despite large genome variation. However, few pathways such as tetrahydrofolate biosynthesis were found to be variable and could be contributing to adaptation towards virulence such as antibiotic resistance.