EAT-2 attenuates C. elegans development via metabolic remodeling in a chemically defined food environment.

Dietary intake and nutrient composition regulate animal growth and development; however, the underlying mechanisms remain elusive. Our previous study has shown that either the mammalian deafness homolog gene tmc-1 or its downstream acetylcholine receptor gene eat-2 attenuates Caenorhabditis elegans development in a chemically defined food CeMM (C. elegans maintenance medium) environment, but the underpinning mechanisms are not well-understood. Here, we found that, in CeMM food environment, for both eat-2 and tmc-1 fast-growing mutants, several fatty acid synthesis and elongation genes were highly expressed, while many fatty acid ß-oxidation genes were repressed. Accordingly, dietary supplementation of individual fatty acids, such as monomethyl branch chain fatty acid C17ISO, palmitic acid and stearic acid significantly promoted wild-type animal development on CeMM, and mutations in either C17ISO synthesis gene elo-5 or elo-6 slowed the rapid growth of eat-2 mutant. Tissue-specific rescue experiments showed that elo-6 promoted animal development mainly in the intestine. Furthermore, transcriptome and metabolome analyses revealed that elo-6/C17ISO regulation of C. elegans development may be correlated with up-regulating expression of cuticle synthetic and hedgehog signaling genes, as well as promoting biosynthesis of amino acids, amino acid derivatives and vitamins. Correspondingly, we found that amino acid derivative S-adenosylmethionine and its upstream metabolite methionine sulfoxide significantly promoted C. elegans development on CeMM. This study demonstrated that C17ISO, palmitic acid, stearic acid, S-adenosylmethionine and methionine sulfoxide inhibited or bypassed the TMC-1 and EAT-2-mediated attenuation of development via metabolic remodeling, and allowed the animals to adapt to the new nutritional niche.

Multi-Omics Integrative Analysis to Reveal the Impacts of Shewanella algae on the Development and Lifespan of Marine Nematode Litoditis marina.

Understanding how habitat bacteria affect animal development, reproduction, and aging is essential for deciphering animal biology. Our recent study showed that Shewanella algae impaired Litoditis marina development and lifespan, compared with Escherichia coli OP50 feeding; however, the underlying mechanisms remain unclear. Here, multi-omics approaches, including the transcriptome of both L. marina and bacteria, as well as the comparative bacterial metabolome, were utilized to investigate how bacterial food affects animal fitness and physiology. We found that genes related to iron ion binding and oxidoreductase activity pathways, such as agmo-1, cdo-1, haao-1, and tdo-2, were significantly upregulated in L. marina grown on S. algae, while extracellular structural components-related genes were significantly downregulated. Next, we observed that bacterial genes belonging to amino acid metabolism and ubiquinol-8 biosynthesis were repressed, while virulence genes were significantly elevated in S. algae. Furthermore, metabolomic analysis revealed that several toxic metabolites, such as puromycin, were enriched in S. algae, while many nucleotides were significantly enriched in OP50. Moreover, we found that the "two-component system" was enriched in S. algae, whereas "purine metabolism" and "one-carbon pool by folate" were significantly enriched in E. coli OP50. Collectively, our data provide new insights to decipher how diet modulates animal fitness and biology.

Transcriptome Responses to Different Salinity Conditions in Litoditis marina, Revealed by Long-Read Sequencing.

The marine nematode Litoditis marina is widely distributed in intertidal zones around the globe, yet the mechanisms underlying its broad adaptation to salinity remain elusive. In this study, we applied ONT long-read sequencing technology to unravel the transcriptome responses to different salinity conditions in L. marina. Through ONT sequencing under 3‱, 30‱ and 60‱ salinity environments, we obtained 131.78 G clean data and 26,647 non-redundant long-read transcripts, including 6464 novel transcripts. The DEGs obtained from the current ONT lrRNA-seq were highly correlated with those identified in our previously reported Illumina short-read RNA sequencing data. When we compared the 30‱ to the 3‱ salinity condition, we found that GO terms such as oxidoreductase activity, cation transmembrane transport and ion transmembrane transport were shared between the ONT lrRNA-seq and Illumina data. Similarly, GO terms including extracellular space, structural constituents of cuticle, substrate-specific channel activity, ion transport and substrate-specific transmembrane transporter activity were shared between the ONT and Illumina data under 60‱ compared to 30‱ salinity. In addition, we found that 79 genes significantly increased, while 119 genes significantly decreased, as the salinity increased. Furthermore, through the GO enrichment analysis of 214 genes containing DAS, in 30‱ compared to 3‱ salinity, we found that GO terms such as cellular component assembly and coenzyme biosynthetic process were enriched. Additionally, we observed that GO terms such as cellular component assembly and coenzyme biosynthetic process were also enriched in 60‱ compared to 30‱ salinity. Moreover, we found that 86, 125, and 81 genes that contained DAS were also DEGs, in comparisons between 30‱ and 3‱, 60‱ and 30‱, and 60‱ and 3‱ salinity, respectively. In addition, we demonstrated the landscape of alternative polyadenylation in marine nematode under different salinity conditions This report provides several novel insights for the further study of the mechanisms by which euryhalinity formed and evolved, and it might also contribute to the investigation of salinity dynamics induced by global climate change.