Li, J. L. | Search bioRxiv

bioRxiv2019

Global Analysis of Human mRNA Folding Disruptions in Synonymous Variants Demonstrates Significant Population Constraint

BackgroundIn most organisms the structure of an mRNA molecule is crucial in determining speed of translation, half-life, splicing propensities and final protein configuration. Synonymous variants which distort this wildtype mRNA structure may be pathogenic as a consequence. However, current clinical guidelines classify synonymous or "silent" single nucleotide variants (sSNVs) as largely benign unless a role in RNA splicing can be demonstrated. ResultsWe developed novel software to conduct a global transcriptome study in which RNA folding statistics were computed for 469 million SNVs in 45,800 transcripts using an Apache Spark implementation of ViennaRNA in the cloud. Focusing our analysis on the subset of 17.9 million sSNVs, we discover that variants predicted to disrupt mRNA structure have lower rates of incidence in the human population. Given that the community lacks tools to evaluate the potential pathogenic impact of sSNVs, we introduce a "Structural Predictivity Index" (SPI) to quantify this constraint due to mRNA structure. ConclusionsOur findings support the hypothesis that sSNVs may play a role in genetic disorders due to their effects on mRNA structure. Our RNA-folding scores provide a means of gauging the structural constraint operating on any sSNV in the human genome. Given that the majority of patients with rare or as yet to be diagnosed disease lack a molecular diagnosis, these scores have the potential to enable discovery of novel genetic etiologies. Our RNA Stability Pipeline as well as ViennaRNA structural metrics and SPI scores for all human synonymous variants can be downloaded from GitHub https://github.com/nch-igm/rna-stability.

genomics↗

bioRxiv2018

Influence of food and Nosema ceranae infection on the gut microbiota of Apis cerana workers

BackgroundGut microbiota plays an essential role in bees health. To elucidate the effect of food and Nosema ceranae infection on the gut microbiota of honeybee Apis cerana, we used 16S rRNA sequencing to survey the gut microbiota of honeybee workers fed with sugar water or beebread and inoculated with or without N. ceranae.\n\nResultsThe gut microbiota of A. cerana is dominated by Serratia, Snodgrassella, and Lactobacillus genera. The overall gut microbiota diversity was significantly differential by food type. The N. ceranae infection significantly affects the gut microbiota only at bees fed with sugar water. Higher abundance of Lactobacillus, Gluconacetobacter and Snodgrassella and lower abundance of Serratia were found in bees fed with beebread than with sugar water. N. ceranae infection led to higher abundance of Snodgrassella and lower abundance of Serratia in sugar-fed bees. Imputed bacterial KEGG pathways showed the significant metagenomics functional differences by feeding and N. ceranae infections. Furthermore, A. cerana workers fed with sugar water showed lower N. ceranae spore loads but higher mortality than those fed with beebread. The cumulative mortality was strongly positive correlated (rho=0.61) with the changes of overall microbiota dissimilarities by N. ceranae infection.\n\nConclusionsBoth food and N. ceranae infection significantly affect the gut microbiota in A. cerana workers. Beebread feeding not only provide better nutrition but also help establish a more stabled gut microbiota therefore protect bee in response to N. ceranae infection.\n\nAbstract ImportanceGut microbiota plays an essential role in bees health. Scientific evidence suggests the diet and infection can affect the gut microbiota and modulate the gut health, however the interplay between those two factors and bee gut microbiota is not well known. In this study, we used high-throughput sequencing method to monitor the changes of gut microbiota by both food intake and the Nosema ceranae infection. Our result showed that the gut microbiota composition and diversity of Asia Honeybee was significantly associated with both food intake and the N. ceranae infection. More interestingly, bees fed with beebread showed higher microbiota stability and less mortality than those fed with sugar water when infected by N. ceranae. Those data suggest the potential role of beebread, not only providing better nutrition but also helping establish a more stabled gut microbiota to protect bee against N. ceranae infection.

microbiology↗