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...

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Summary VarSome.com is a search engine, aggregator and impact analysis tool for human genetic variation and a community-driven project aiming at sharing global expertise on human variants. Availability and implementation VarSome is freely available at http://varsome.com . Supplementary information Supplementary data are available at Bioinformatics online.

SummaryVarSome.com is a search engine, aggregator and impact analysis tool for human genetic variation and a community-driven project aiming at sharing global expertise on human variants.AvailabilityVarSome is freely available at http://varsome.com.

Moonlighting proteins are a subclass of multifunctional proteins whose functions are unrelated. Although they may play important roles in cells, there has been no large-scale method to identify them, nor any effort to characterize them as a group. Here, we propose the first method for the identification of ‘extreme multifunctional' proteins from an interactome as a first step to characterize moonlighting proteins. By combining network topological information with protein annotations, we identify 430 extreme multifunctional proteins (3% of the human interactome). We show that the candidates form a distinct sub-group of proteins, characterized by specific features, which form a signature of extreme multifunctionality. Overall, extreme multifunctional proteins are enriched in linear motifs and less intrinsically disordered than network hubs. We also provide MoonDB, a database containing information on all the candidates identified in the analysis and a set of manually curated human moonlighting proteins.