Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes-more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca(2+) signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes

Background Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. Results Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. Conclusions Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

Darwin's finches, inhabiting the Galápagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin's finch species and two close relatives. Phylogenetic analysis reveals important discrepancies with the phenotype-based taxonomy. We find extensive evidence for interspecific gene flow throughout the radiation. Hybridization has given rise to species of mixed ancestry. A 240 kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial development is strongly associated with beak shape diversity across Darwin's finch species as well as within the medium ground finch (Geospiza fortis), a species that has undergone rapid evolution of beak shape in response to environmental changes. The ALX1 haplotype has contributed to diversification of beak shapes among the Darwin's finches and, thereby, to an expanded utilization of food resources.

Myotonic dystrophy (DM) is a genetic disorder caused by the expression (as RNA) of expanded CTG or CCTG repeats. The alternative splicing factor MBNL1 is sequestered to the expanded RNA repeats, resulting in missplicing of a subset of pre-mRNAs linked to symptoms found in DM patients. Current data suggest that if MBNL1 is released from sequestration, disease symptoms may be alleviated. We identified the small molecules pentamidine and neomycin B as compounds that disrupt MBNL1 binding to CUG repeats in vitro. We show in cell culture that pentamidine was able to reverse the missplicing of 2 pre-mRNAs affected in DM, whereas neomycin B had no effect. Pentamidine also significantly reduced the formation of ribonuclear foci in tissue culture cells, releasing MBNL1 from the foci in the treated cells. Furthermore, pentamidine partially rescued splicing defects of 2 pre-mRNAs in mice expressing expanded CUG repeats.alternative splicing ͉ triplet repeats ͉ MBNL1 ͉ muscleblind-like 1 ͉ RNA repeats M yotonic dystrophy (DM) is an autosomal dominant genetic disorder that is characterized by a variety of symptoms. There are 2 types of myotonic dystrophy, type 1 (DM1) and type 2 (DM2). DM1 is linked to a (CTG) n repeat expansion in the 3Ј untranslated region of the DMPK gene, whereas DM2 is linked to a (CCTG) n repeat expansion in intron 1 of the ZNF9 gene. The current model is that the expanded repeats are toxic on the RNA level, where either repeat can form a stable structured RNA that aberrantly interacts with proteins in the nucleus (for review see refs. 1, 2).One proposed molecular mechanism that may account for the disease symptoms is that, upon transcription of the expansions, either the CUG or CCUG repeats sequester RNA binding proteins from their normal cellular functions. The protein MBNL1 (Muscleblind-like 1) has been shown to bind both expanded CUG and CCUG repeats in vitro (3-5), and colocalize with these expanded repeats in vivo (6-10). MBNL1 is an alternative splicing factor and its sequestration leads to the missplicing of multiple pre-mRNAs in DM, which is thought to give rise to many of the symptoms of the disease. In support of this model, it has been shown that the disruption of the MBNL1 gene or expression of CUG repeats in mice causes symptoms and missplicing similar to those seen in DM patients (11)(12)(13)(14). Furthermore, disease symptoms can be rescued and missplicing of many pre-mRNAs can be reversed in mice expressing CUG repeats by overexpression of MBNL1 (15).Aside from the overexpression of MBNL1, another possible approach to overcoming the sequestration of MBNL1 is to identify small molecules that specifically bind the CUG repeats and competitively release the sequestered MBNL1. As a step toward identifying a small molecule therapeutic for DM, a small library of molecules known to bind structured nucleic acid were screened for their ability to disrupt an MBNL1-CUG repeat interaction in vitro. Two molecules were identified that strongly disrupted the complex in vitro. Further testing showed tha...