The shallow water bivalve Codakia orbicularis lives in symbiotic association with a sulfur-oxidizing bacterium in its gills. The endosymbiont fixes CO 2 and thus generates organic carbon compounds, which support the host's growth. To investigate the uncultured symbiont's metabolism and symbiont-host interactions in detail we conducted a proteogenomic analysis of purified bacteria. Unexpectedly, our results reveal a hitherto completely unrecognized feature of the C. orbicularis symbiont's physiology: the symbiont's genome encodes all proteins necessary for biological nitrogen fixation (diazotrophy). Expression of the respective genes under standard ambient conditions was confirmed by proteomics. Nitrogenase activity in the symbiont was also verified by enzyme activity assays. Phylogenetic analysis of the bacterial nitrogenase reductase NifH revealed the symbiont's close relationship to free-living nitrogen-fixing Proteobacteria from the seagrass sediment. The C. orbicularis symbiont, here tentatively named 'Candidatus Thiodiazotropha endolucinida', may thus not only sustain the bivalve's carbon demands. C. orbicularis may also benefit from a steady supply of fixed nitrogen from its symbiont-a scenario that is unprecedented in comparable chemoautotrophic symbioses. Mutualistic associations between marine invertebrates and sulfur-oxidizing (thiotrophic) bacteria are a well-documented and widespread phenomenon in a variety of sulfidic habitats ranging from hydrothermal vents to shallow-water coastal ecosystems 1-3 . Thioautotrophic symbionts generate energy through sulfide oxidation and provide their hosts with organic carbon. In the Lucinidae, a diverse family of marine bivalves, all members are obligatorily dependent on their bacterial gill endosymbionts after larval development and metamorphosis 4 . The shallowwater lucinid Codakia orbicularis, which lives in the sediment beneath the tropical seagrass Thalassia testudinum along the Caribbean and Western Atlantic coast 5 , harbours a single species of endosymbionts in its gills 6 . The symbiont has been shown to be newly acquired by each clam generation 7,8 from a pool of freeliving symbiosis-competent bacteria in the environment 9 , rather than being inherited from clam parents. C. orbicularis appears not to release its endosymbionts, even under adverse conditions, but can digest them as a source of nutrition [10][11][12] . Moreover, bacterial cell division seems to be inhibited inside the host tissue. The majority of the symbiont population was shown to be polyploid (that is, containing multiple genome copies), while dividing symbiont cell stages are very rarely observed in host bacteriocytes 13 . The host undoubtedly benefits from the symbiont both by way of detoxification of its sulfidic environment and by supply of organic compounds through the bacterial Calvin-Benson cycle. It remains questionable, however, whether the symbiont gains any advantage from this association in evolutionary terms 11 .Biological nitrogen fixation (diazotrophy) is the conversion of ...
Recurrent spontaneous abortion (RSA) is a common cause of infertility, but previous attempts at identifying RSA causative genes have been relatively unsuccessful. Such failure to describe RSA aetiological genes might be explained by the fact that reproductive phenotypes should be considered as quantitative traits resulting from the intricate interaction of numerous genetic, epigenetic and environmental factors. Here, we studied an interspecific recombinant congenic strain (IRCS) of Mus musculus from the C57BL6/J strain of mice harbouring an approximate 5 Mb DNA fragment from chromosome 13 from Mus spretus mice (66H-MMU13 strain), with a high rate of embryonic resorption (ER). Transcriptome analyses of endometrial and placental tissues from these mice showed a deregulation of many genes associated with the coagulation and inflammatory response pathways. Bioinformatics approaches led us to select Foxd1 as a candidate gene potentially related to ER and RSA. Sequencing analysis of Foxd1 in the 66H-MMU13 strain, and in 556 women affected by RSA and 271 controls revealed non-synonymous sequence variants. In vitro assays revealed that some led to perturbations in FOXD1 transactivation properties on promoters of genes having key roles during implantation/placentation, suggesting a role of this gene in mammalian implantation processes.
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