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1. ToxCodAn-Genome: an automated pipeline for toxin-gene annotation in genome assembly of venomous lineages

   https://doi.org/10.1093/gigascience/giad116  

   Nachtigall, Pedro_G ; Durham, Alan_M ; Rokyta, Darin_R ; Junqueira-de-Azevedo, Inácio_L_M ( January 2024 , GigaScience)

   The rapid development of sequencing technologies resulted in a wide expansion of genomics studies using venomous lineages. This facilitated research focusing on understanding the evolution of adaptive traits and the search for novel compounds that can be applied in agriculture and medicine. However, the toxin annotation of genomes is a laborious and time-consuming task, and no consensus pipeline is currently available. No computational tool currently exists to address the challenges specific to toxin annotation and to ensure the reproducibility of the process.

   Here, we present ToxCodAn-Genome, the first software designed to perform automated toxin annotation in genomes of venomous lineages. This pipeline was designed to retrieve the full-length coding sequences of toxins and to allow the detection of novel truncated paralogs and pseudogenes. We tested ToxCodAn-Genome using 12 genomes of venomous lineages and achieved high performance on recovering their current toxin annotations. This tool can be easily customized to allow improvements in the final toxin annotation set and can be expanded to virtually any venomous lineage. ToxCodAn-Genome is fast, allowing it to run on any personal computer, but it can also be executed in multicore mode, taking advantage of large high-performance servers. In addition, we provide a guide to direct future research in the venomics field to ensure a confident toxin annotation in the genome being studied. As a case study, we sequenced and annotated the toxin repertoire of Bothrops alternatus, which may facilitate future evolutionary and biomedical studies using vipers as models.

   ToxCodAn-Genome is suitable to perform toxin annotation in the genome of venomous species and may help to improve the reproducibility of further studies. ToxCodAn-Genome and the guide are freely available at https://github.com/pedronachtigall/ToxCodAn-Genome.

    

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2. Natural methylation epialleles correlate with gene expression in maize

   https://doi.org/10.1093/genetics/iyad146  

   Zeng, Yibing ; Dawe, R Kelly ; Gent, Jonathan I ( August 2023 , GENETICS)

   Bomblies, K (Ed.)

   DNA methylation in plants is depleted from cis-regulatory elements in and near genes but is present in some gene bodies, including exons. Methylation in exons solely in the CG context is called gene body methylation (gbM). Methylation in exons in both CG and non-CG contexts is called TE-like methylation (teM). Assigning functions to both forms of methylation in genes has proven to be challenging. Toward that end, we utilized recent genome assemblies, gene annotations, transcription data, and methylome data to quantify common patterns of gene methylation and their relations to gene expression in maize. We found that gbM genes exist in a continuum of CG methylation levels without a clear demarcation between unmethylated genes and gbM genes. Analysis of expression levels across diverse maize stocks and tissues revealed a weak but highly significant positive correlation between gbM and gene expression except in endosperm. gbM epialleles were associated with an approximately 3% increase in steady-state expression level relative to unmethylated epialleles. In contrast to gbM genes, which were conserved and were broadly expressed across tissues, we found that teM genes, which make up about 12% of genes, are mainly silent, are poorly conserved, and exhibit evidence of annotation errors. We used these data to flag teM genes in the 26 NAM founder genome assemblies. While some teM genes are likely functional, these data suggest that the majority are not, and their inclusion can confound the interpretation of whole-genome studies.

    

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3. Prevalent use and evolution of exonic regulatory sequences in the human genome

   https://doi.org/10.1002/ntls.20220058  

   Chen, Jing ; Ni, Pengyu ; Wu, Siwen ; Niu, Meng ; Guo, Jun‐tao ; Su, Zhengsheng ( March 2023 , Natural Sciences)

   It has long been known that exons can serve ascis‐regulatory sequences, such as enhancers. However, the prevalence of such dual‐use of exons and how they evolve remain elusive. Based on our recently predicted, highly accurate large sets ofcis‐regulatory module candidates (CRMCs) and non‐CRMCs in the human genome, we find that exonic transcription factor binding sites (TFBSs) occupy at least a third of the total exon lengths, and 96.7% of genes have exonic TFBSs. Both A/T and C/G in exonic TFBSs are more likely under evolutionary constraints than those in non‐CRMC exons. Exonic TFBSs in codons tend to encode loops rather than more critical helices and strands in protein structures, while exonic TFBSs in untranslated regions (UTRs) tend to avoid positions where known UTR‐related functions are located. Moreover, active exonic TFBSs tend to be in close physical proximity to distal promoters whose genes have elevated transcription levels. These results suggest that exonic TFBSs might be more prevalent than originally thought and likely in dual‐use. We proposed a parsimonious model that well explains the observed evolutionary behaviors of exonic TFBS as well as how a stretch of codons evolve into a TFBS.

   There are more exonic regulatory sequences in the human genome than originally thought.

   Exonic transcription factor binding sites are more likely under negative selection or positive selection than counterpart nonregulatory sequences.

   Exonic transcription factor binding sites tend to be located in genome sequences that encode less critical loops in protein structures, or in less critical parts in 5′ and 3′ untranslated regions.

    

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4. Effect of gut microbiota on α‐amanitin tolerance in Drosophila tripunctata

   https://doi.org/10.1002/ece3.6630  

   Griffin, Logan H. ; Reed, Laura K. ( August 2020 , Ecology and Evolution)

   The bacterial gut microbiota of many animals is known to be important for many physiological functions including detoxification. The selective pressures imposed on insects by exposure to toxins may also be selective pressures on their symbiotic bacteria, who thus may contribute to the mechanism of toxin tolerance for the insect. Amatoxins are a class of cyclopeptide mushroom toxins that primarily act by binding to RNA polymerase II and inhibiting transcription. Several species of mycophagousDrosophilaare tolerant to amatoxins found in mushrooms of the genusAmanita, despite these toxins being lethal to most other known eukaryotes. These species can tolerate amatoxins in natural concentrations to utilize toxic mushrooms as larval hosts, but the mechanism by which these species are tolerant remains unknown. Previous data have shown that a local population ofD. tripunctataexhibits significant genetic variation in toxin tolerance. This study assesses the potential role of the microbiome in α‐amanitin tolerance in six wild‐derived strains ofDrosophila tripunctata. Normal and antibiotic‐treated samples of six strains were reared on diets with and without α‐amanitin, and then scored for survival from the larval stage to adulthood and for development time to pupation. Our results show that a substantial reduction in bacterial load does not influence toxin tolerance in this system, while confirming genotype and toxin‐specific effects on survival are independent of the microbiome composition. Thus, we conclude that this adaptation to exploit toxic mushrooms as a host is likely intrinsic to the fly's genome and not a property of their microbiome.

    

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5. A semi-analytical model for the propagation of a relativistic jet in a magnetized medium

   https://doi.org/10.1093/mnras/stae1348  

   García-García, Leonardo ; López-Cámara, Diego ; Lazzati, Davide ( May 2024 , Monthly Notices of the Royal Astronomical Society)

   The merger of two magnetized compact objects, such as neutron stars, forms a compact object which may launch a relativistic and collimated jet. Numerical simulations of the process show that a dense and highly magnetized medium surrounds the system. This study presents a semi-analytical model that models the effects that a static magnetized medium with a tangled field produces in relativistic, collimated, and non-magnetized jets. The model is a first approximation that addresses the magnetic field present in the medium and is based on pressure equilibrium principles between the jet, cocoon, and external medium. A fraction of the ambient medium field is allowed to be entrained in the cocoon. We find that the jet and cocoon properties may be affected by high magnetic fields (≳ 1015 G) and mixing. The evolution of the system may vary up to $\sim 10{{\ \rm per\ cent}}$ (compared to the non-magnetized case). Low-mixing may produce a slower broader jet with a broader and more energetic cocoon would be produced. On the other hand, high-mixing could produce a faster narrower jet with a narrow and less-energetic cocoon. Two-dimensional hydrodynamical simulations are used to validate the model and to constrain the mixing parameter. Although the magnetic field and mixing have a limited effect, our semi-analytic model captures the general trend consistent with numerical results. For high magnetization, the results were found to be more consistent with the low mixing case in our semi-analytic model.

    

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