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Johansen, M.

Publications and source records attributed to Johansen, M..

6 recordsLinked to original sources

Massive programmed DNA elimination during embryogenesis in the trioecious nematode Auanema rhodense

In animals, the germline is usually set aside early in development and its genome is protected to ensure faithful transmission of genetic information to future generations. Genetic alterations in somatic cells are not inherited by progeny, and the somatic genome does not have to be protected from change in the same way. In some species, programmed DNA elimination (PDE) results in the directed loss of genetic material from somatic cells. Here, we report extreme PDE in Auanema rhodense, a free-living nematode with a remarkable, trioecious life history and unusual patterns of sex chromosome inheritance. We find that nearly two thirds of the A. rhodense germline genome is eliminated from somatic cells, with DNA lost from chromosome ends as well as within chromosomes, resulting in fragmentation of the seven germline chromosomes into fourteen somatic chromosomes. Most eliminated DNA comprises multi-megabase tandem repeat blocks. Eliminated DNA on the X chromosome harbours germline-restricted repeats that are distinct from those on the autosomes. The eliminated DNA includes many highly-repeated non-coding RNA loci but few protein-coding genes. Elimination sites are strongly associated with a palindromic sequence motif that likely directs DNA breakage and new telomere repeat array addition. Cytologically, PDE begins at the 12-cell stage of embryogenesis, is synchronous across all chromosomes, and is characterised by the formation of transient micronucleus-like bodies. Together, these findings reveal unusually extensive PDE in a free-living nematode and raise the possibility that germline-restricted repeat architecture may contribute to the atypical sex chromosome inheritance observed in Auanema.

genomics↗

An ancient polymorphism in myosin I a/b determines the left-right asymmetry of Japanese snails

Left-right (LR) asymmetry is a fundamental feature of animal development, yet progress in understanding its establishment has been limited by the fact that almost all animals exhibit invariant chirality. Snails are the exception because some wild-living species show abundant chiral variation, yet the existing knowledge is from snails in which the chirality mutation is rare and causes pathology. Here, we show that a chiral polymorphism in Japanese Euhadra snails is due to functional variation in an unconventional myosin I a/b, an isoform not previously implicated in LR specification in any animal. Both the sinistral and dextral gene variants are ancient, impart minimal transcriptional differences in the single-cell embryo and are not pathological. Phylogenetic and structural modelling suggests that dominant-acting amino acid substitutions in the myosin actin-binding domain and/or motor-level junction were enabled by relaxed selection. These results broaden the known molecular repertoire underlying LR asymmetry, suggest key mutations and positions that should be explored in other model animals, and highlight snails as a powerful model for understanding the origins of animal LR asymmetry.

evolutionary biology↗

Environmental identification of novel enzymes against heteroatomic plastics

Better enzymes are needed to develop sustainable methods to recycle plastics with C-X heterobonds such as polyurethane (PUR) and nylon, for which no industrial-scale solutions exist. Current methods rely largely on sequence mining based on a small number of known enzymes. Here we expand the pool of PURases and nylonases by bioprospecting legacy plastic waste with fluorophore plastic mimics combined with FACS. We identify 29 plastic-degrading bacteria, from which 12 enzymes are identified by mass spectrometry and homology searches. Compared to existing enzymes, these enzymes are superior in thermostability and the ability to hydrolyse different high-molecular weight PUR oligomers and nylon textiles. To our knowledge, this is the first reported example of enzymes capable of hydrolysing longer chains of PUR and nylon. This study significantly increases the number of known PURases and nylonases and provides starting points for optimization campaigns through protein engineering and for in silico discovery.

biochemistry↗

A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should aim to elicit broad-protection, provide long-lasting immunity and facilitate equitable access for all populations. In this study, a panel of chimeric, full-length spike antigens were developed that incorporate mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was obtained from a high-yield production process in stable CHO cells with purity of >95%, long-term stability and elicitation of broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced protein vaccine (NVX-CoV2373), CoVEXS5 could boost T cell immunity, as well as neutralising antibodies levels against viruses from three sarbecoviruses clades. The breadth of sarbecovirus cross-reactivity elicited by CoVEXS5 exceeded that observed after boosting with the NVX-CoV2373 vaccine. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.

immunology↗

MirGeneDB 3.0: Improved taxonomic sampling, uniform nomenclature of novel conserved microRNA families, and updated covariance models.

We present a major update of MirGeneDB (3.0), the manually curated animal microRNA gene database. Beyond moving to a new server and the creation of a computational mirror, we have expanded the database with the addition of 33 invertebrate species, including representatives of 5 previously unsampled phyla, and 6 mammal species. MirGeneDB now contains entries for 21, 822 microRNA genes (5, 160 of these from the new species) belonging to 1743 microRNA families. The inclusion of these new species allowed us to refine both the evolutionary node of appearance of a number of microRNA genes/families, as well as MirGeneDBs phylogenetically informed nomenclature system. Updated covariance models of all microRNA families, along with all smallRNA read data are now downloadable. These enhanced annotations will allow researchers to analyze microRNA properties such as secondary structure and features of their biogenesis within a robust phylogenetic context and without the database plagued with numerous false positives and false negatives. In light of these improvements, MirGeneDB 3.0 will assume the responsibility for naming conserved novel metazoan microRNAs. MirGeneDB is part of RNAcentral and Elixir Norway, and is publicly and freely available at master.cloud.mirgenedb.org. Key PointsO_LIMajor update to the manually curated and uniformly named microRNA gene database MirGeneDB C_LIO_LI114 animal species, >1700 microRNA families and [~]20 000 genes searchable, browsable and downloadable C_LIO_LINew features to download all smallRNA read data and updated covariance models for each family C_LI

evolutionary biology↗

MirGeneDB2.0: the curated microRNA Gene Database

Small non-coding RNAs have gained substantial attention due to their roles in animal development and human disorders. Among them, microRNAs are unique because individual gene sequences are conserved across the animal kingdom. In addition, unique and mechanistically well understood features can clearly distinguish bona fide miRNAs from the myriad other small RNAs generated by cells. However, making this separation is not a common practice and, thus, not surprisingly, the heterogeneous quality of available miRNA complements has become a major concern in microRNA research. We addressed this by extensively expanding our curated microRNA gene database MirGeneDB to 45 organisms that represent the full taxonomic breadth of Metazoa. By consistently annotating and naming more than 10,900 microRNA genes in these organisms, we show that previous microRNA annotations contained not only many false positives, but surprisingly lacked more than 2,100 bona fide microRNAs. Indeed, curated microRNA complements of closely related organisms are very similar and can be used to reconstruct Metazoan evolution. MirGeneDB represents a robust platform for microRNA-based research, providing deeper and more significant insights into the biology and evolution of miRNAs but also biomedical and biomarker research. MirGeneDB is publicly and freely available at http://mirgenedb.org/.

genomics↗