Tetraodon nigroviridis is a freshwater puffer fish with the smallest known vertebrate genome. Here, we report a draft genome sequence with long-range linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome analysis provides a greatly improved fish gene catalogue, including identifying key genes previously thought to be absent in fish. Comparison with other vertebrates and a urochordate indicates that fish proteins have diverged markedly faster than their mammalian homologues. Comparison with the human genome suggests ,900 previously unannotated human genes. Analysis of the Tetraodon and human genomes shows that whole-genome duplication occurred in the teleost fish lineage, subsequent to its divergence from mammals. The analysis also makes it possible to infer the basic structure of the ancestral bony vertebrate genome, which was composed of 12 chromosomes, and to reconstruct much of the evolutionary history of ancient and recent chromosome rearrangements leading to the modern human karyotype.Access to entire genome sequences is revolutionizing our understanding of how genetic information is stored and organized in DNA, and how it has evolved over time. The sequence of a genome provides exquisite detail of the gene catalogue within a species, and the recent analysis of near-complete genome sequences of three mammals (human 1 , mouse 2 and rat 3 ) shows the acceleration in the search for causal links between genotype and phenotype, which can then be related to physiological, ecological and evolutionary observations. The partial sequence of the compact puffer fish Takifugu rubripes genome was obtained recently and this survey provided a preliminary catalogue of fish genes 4 . However, the Takifugu assembly is highly fragmented and as a result important questions could not be addressed.Here, we describe and analyse the genome sequence of the freshwater puffer fish Tetraodon nigroviridis with long-range linkage and extensive anchoring to chromosomes. Tetraodon resembles Takifugu in that it possesses one of the smallest known vertebrate genomes, but as a popular aquarium fish it is readily available and is easily maintained in tap water (see Supplementary Notes for naming conventions, natural habitat and phylogeny). The two puffer fish diverged from a common ancestor between 18-30 million years (Myr) ago and from the common ancestor with mammals about 450 Myr ago 5 . This long evolutionary distance provides a good contrast to distinguish conserved features from neutrally evolving DNA by sequence comparison. Tetraodon sequences in fact had an important role in providing a reliable estimate of the number of genes in the human genome 6 . There has been a vigorous and unresolved debate as to whether a whole-genome duplication (WGD) occurred in the ray-finned fish (actinopterygians) lineage after its separation from tetrapods [7][8][9] . By exploiting the extensive anchoring of the Tetraodon sequence to chromosomes, we provide a definitive answer to this question. The distribution of duplicated genes in t...
Mycobacterium abscessus is a rapidly growing Mycobacterium causing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. The M. abscessus rough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth (S) variant, but the underlying mechanisms of R-variant virulence remain obscure. Exploiting the optical transparency of zebrafish embryos, we observed that the increased virulence of the M. abscessus R variant compared with the S variant correlated with the loss of GPL production. The virulence of the R variant involved the massive production of serpentine cords, absent during S-variant infection, and the cords initiated abscess formation leading to rapid larval death. Cording occurred within the vasculature and was highly pronounced in the central nervous system (CNS). It appears that M. abscessus is transported to the CNS within macrophages. The release of M. abscessus from apoptotic macrophages initiated the formation of cords that grew too large to be phagocytized by macrophages or neutrophils. This study is a description of the crucial role of cording in the in vivo physiopathology of M. abscessus infection and emphasizes cording as a mechanism of immune evasion.morphotype | pathogenesis | granuloma | innate immunity T he rapidly growing mycobacterium (RGM) Mycobacterium abscessus (M. abscessus) is an emerging pathogen that infects a wide spectrum of tissues in humans, including lungs, skin, and soft tissues (1, 2). M. abscessus lung disease is highly prevalent in patients with cystic fibrosis (CF) and is becoming a major issue for most CF centers worldwide (3-6). Although M. abscessus is an RGM, it can persist and cause lung disease with caseous lesions (7).M. abscessus exists as two variants: rough (R) and smooth (S). Ex vivo and in vivo studies have described the hypervirulence phenotype of the R versus the S morphotype (8, 9), and epidemiological studies have confirmed the persistence and acute respiratory syndromes caused by the R morphotype (4, 10, 11). The major difference between the R and S variants is the loss of a surface-associated glycopeptidolipid (GPL) (12). Analysis of the pathogenicity of M. abscessus has been hampered by the lack of genetic tools and the restricted panel of cellular/animal models. However, new genetic tools, including conditional gene expression, recently have been applied to both the S and R morphotypes (13, 14), but developing new animal models amenable to the manipulation of the host response is still challenging. The M. abscessus genome harbors a mercury-resistance plasmid sharing 99% identity with an episome from the slowgrowing fish pathogen Mycobacterium marinum, indicating that these species have exchanged this plasmid in a shared ecosystem (15). M. abscessus has been described in wild and captive fish species (16,17), and hand infections caused by M. abscessus have been reported in healthy fish handlers (18), sug...
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