Ammonia-oxidizing archaea (AOA) of the phylum Thaumarchaeota are widespread in marine and terrestrial habitats, playing a major role in the global nitrogen cycle. However, their evolutionary history remains unexplored, which limits our understanding of their adaptation mechanisms. Here, our comprehensive phylogenomic tree of Thaumarchaeota supports three sequential events: origin of AOA from terrestrial non-AOA ancestors, colonization of the shallow ocean, and expansion to the deep ocean. Careful molecular dating suggests that these events coincided with the Great Oxygenation Event around 2300 million years ago (Mya), and oxygenation of the shallow and deep ocean around 800 and 635-560 Mya, respectively. The first transition was likely enabled by the gain of an aerobic pathway for energy production by ammonia oxidation and biosynthetic pathways for cobalamin and biotin that act as cofactors in aerobic metabolism. The first transition was also accompanied by the loss of dissimilatory nitrate and sulfate reduction, loss of oxygen-sensitive pyruvate oxidoreductase, which reduces pyruvate to acetyl-CoA, and loss of the Wood-Ljungdahl pathway for anaerobic carbon fixation. The second transition involved gain of a K + transporter and of the biosynthetic pathway for ectoine, which may function as an osmoprotectant. The third transition was accompanied by the loss of the uvr system for repairing ultraviolet light-induced DNA lesions. We conclude that oxygen availability drove the terrestrial origin of AOA and their expansion to the photic and dark oceans, and that the stressors encountered during these events were partially overcome by gene acquisitions from Euryarchaeota and Bacteria, among other sources.

Surface ocean waters are dominated by planktonic bacterial lineages with highly reduced genomes. The best examples are the cyanobacterial genus Prochlorococcus, the alphaproteobacterial clade SAR11 and the gammaproteobacterial clade SAR86, which together represent over 50% of the cells in surface oceans. Several studies have identified signatures of selection on these lineages in today's ocean and have postulated selection as the primary force throughout their evolutionary history. However, massive loss of genomic DNA in these lineages often occurred in the distant past, and the selective pressures underlying these ancient events have not been assessed. Here, we probe ancient selective pressures by computing %GC-corrected rates of conservative and radical nonsynonymous nucleotide substitutions. Surprisingly, we found an excess of radical changes in several of these lineages in comparison to their relatives with larger genomes. Furthermore, analyses of allelic genome sequences of several populations within these lineages consistently supported that radical replacements are more likely to be deleterious than conservative changes. Our results suggest coincidence of massive genomic DNA losses and increased power of genetic drift, but we also suggest that additional evidence independent of the nucleotide substitution analyses is needed to support a primary role of genetic drift driving ancient genome reduction of marine bacterioplankton lineages.

An important unanswered question in evolutionary genomics is the source of considerable variation of genomic base composition (GC content) even among organisms that share one habitat. Evolution toward GC-poor genomes has been considered a major adaptive pathway in the oligotrophic ocean, but GC-rich bacteria are also prevalent and highly successful in this environment. We quantify the contribution of multiple factors to the change of genomic GC content of Ruegeria pomeroyi DSS-3, a representative and GC-rich member in the globally abundant Roseobacter clade, using an agent-based model. The model simulates 2 × 10 cells, which allows random genetic drift to act in a realistic manner. Each cell has a whole genome subject to base-substitution mutation and recombination, which affect the carbon and nitrogen requirements of DNA and protein pools. Nonsynonymous changes can be functionally deleterious. Together, these factors affect the growth and fitness. Simulations show that experimentally determined mutation bias toward GC is not sufficient to build the GC-rich genome of DSS-3. While nitrogen availability has been repeatedly hypothesized to drive the evolution of GC content in marine bacterioplankton, our model instead predicts that DSS-3 and its ancestors have been evolving in environments primarily limited by carbon.

Summary The taxonomy of marine and non‐marine organisms rarely overlap, but the mechanisms underlying this distinction are often unknown. Here, we predicted three major ocean‐to‐land transitions in the evolutionary history of Flavobacteriaceae, a family known for polysaccharide and peptide degradation. These unidirectional transitions were associated with repeated losses of marine signature genes and repeated gains of non‐marine adaptive genes. This included various Na+‐dependent transporters, osmolyte transporters and glycoside hydrolases (GH) for sulfated polysaccharide utilization in marine descendants, and in non‐marine descendants genes for utilizing the land plant material pectin and genes facilitating terrestrial host interactions. The K+ scavenging ATPase was repeatedly gained whereas the corresponding low‐affinity transporter repeatedly lost upon transitions, reflecting K+ ions are less available to non‐marine bacteria. Strikingly, the central metabolism Na+‐translocating NADH: quinone dehydrogenase gene was repeatedly gained in marine descendants, whereas the H+‐translocating counterpart was repeatedly gained in non‐marine lineages. Furthermore, GH genes were depleted in isolates colonizing animal hosts but abundant in bacteria inhabiting other non‐marine niches; thus relative abundances of GH versus peptidase genes among Flavobacteriaceae lineages were inconsistent with the marine versus non‐marine dichotomy. We suggest that phylogenomic analyses can cast novel light on mechanisms explaining the distribution and ecology of key microbiome components.

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This study was carried out to investigate the effects of resveratrol on cigarette smoke (CS)-induced lung injury. Experimental mice were administrated with 1 mg/kg or 3 mg/ kg resveratrol orally, 1 h prior to CS exposure (five cigarettes a day for 3 consecutive days). Airway inflammation and gene expression changes were assessed. CS exposure increased the number of pulmonary inflammatory cells, coupled with elevated production of tumor necrosis factor α and interleukin-6 in bronchoalveolar lavage fluids. Resveratrol treatment decreased CS-induced lung inflammation. Resveratrol restored the activities of superoxide dismutase, GSH peroxidase, and catalase in CS-treated mice. CS significantly enhanced the nuclear translocation of nuclear factor κB (NF-κB) and NF-κB DNA binding activity, which was impaired by resveratrol pretreatment. In addition, resveratrol promoted CS-induced heme oxygenase-1 (HO-1) expression and activation. Our results collectively indicate that resveratrol attenuates CS-induced lung oxidative injury, which involves decreased NF-κB activity and the elevated HO-1 expression and activity.

BackgroundAccumulating evidence has emphasized causative links between aberrant microRNA (miR) expression patterns and cancer development. Abnormally expressed miRNA-98 (miR-98) was found in certain types of human cancers. The biological roles of miR-98 in lung cancer, however, remain largely undefined.MethodsWe evaluated the expression of miR-98 in normal lung tissues, lung cancer tissues, normal human bronchial epithelial cells, and lung cancer cells using quantitative real-time polymerase chain reaction. Effect of miR-98 on proliferation of lung cancer cells was investigated using MTT assay and colony formation assay. Transwell assay was used to assess the effects of miR-98 on migration and invasion of lung cancer cells. Whether miR-98 targets the 3′-untranslated region (3′-UTR) of integrin β3 (ITGB3) coding gene ITGB3 mRNA was ascertained using luciferase reporter assay. Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth in vivo.ResultsWe confirmed that miR-98 was frequently low expressed in lung cancer tissues and human lung cancer cells. Reintroduction of miR-98 into lung cancer cells inhibited cell proliferation, migration, and invasion in vitro and suppressed tumor formation in a nude mouse model. Furthermore, we identified that miR-98 exerted inhibitory roles by directly binding to 3′-UTR of ITGB3 mRNA, thus negatively regulated the expression of ITGB3. Interestingly, upon restoring the expression of ITGB3, the effect of miR-98 on cell proliferation was partially reversed.ConclusionOur findings suggest that miR-98 prevents proliferation, migration, and invasion of lung cancer cells by directly binding to the 3′-UTR of ITGB3 mRNA and could be a promising treatment option in anticancer therapy.

Cervical cancer is the most common cause of cancer-related deaths in women from developing countries. Identification of novel prognostic predictors or therapeutic targets may improve patient prognosis. In the current study, we demonstrated by real-time PCR that miR-224 expression was significantly upregulated (1.82-fold, P = 0.0025) in cervical cancer tissues (n = 126) compared with in normal cervical tissues (n = 64). Higher expression of miR-224 was significantly associated with poorer prognostic factors, including advanced FIGO stage, nodal metastasis, larger tumor size, vascular involvement and deep stromal invasion (all P < 0.05). Enforced expression of miR-224 promoted cell proliferation, migration and invasion in SiHa and CaSki cancer cell lines. Bioinformatic analysis indicated that RASSF8 (RAS-association domain family 8) was a potential target of miR-224. Western blot analysis and luciferase reporter assay showed that overexpressed miR-224 inhibited RASSF8 protein expression and decreased the activity of a luciferase reporter containing the 3′ untranslated region (UTR) of RASSF8, respectively. Further, RASSF8 knockdown by specific RNAi showed similar effects in cervical cancer cells transfected with miR-224 mimic. Our findings suggest that miR-224 directly targets RASSF8 and thereby acts as a tumor promoter in cervical cancer progression.