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We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.

BackgroundArthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.ResultsUsing 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception.ConclusionsThese analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.

Opisthorchiasis is a neglected tropical disease of major proportion, caused by the carcinogenic, Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is known to be associated with malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Southeast Asia. No vaccine is available, and only one drug (praziquantel) is routinely employed against the parasite. Despite technological advances, little is known about the molecular biology of the fluke itself and the disease complex that it causes in humans. The advent of high-throughput nucleic acid sequencing and bioinformatic technologies is enabling researchers to gain global insights into the molecular pathways and processes in parasites. The principal aims of this chapter are to (1) review molecular research of O. viverrini and opisthorchiasis; (2) provide an account of recent advances in the sequencing and characterization of the genome and transcriptomes of O. viverrini; (3) describe the complex life of this worm in the biliary system of the definitive (human) host and how the fluke interacts with this host and causes disease at the molecular level; (4) discuss the implications of systems biological research and (5) consider how progress in genomics and informatics might enable explorations of O. viverrini and related worms and the discovery of new interventions against opisthorchiasis and CCA. [ABSTRACT FROM AUTHOR]

Haemonchus contortus (the barber's pole worm)—a highly pathogenic gastric nematode of ruminants—causes significant economic losses in the livestock industry worldwide. H. contortus has become a valuable model organism for both fundamental and applied research (e.g., drug and vaccine discovery) because of the availability of well-defined laboratory strains (e.g., MHco3(ISE).N1 in the UK and Haecon-5 in Australia) and genomic, transcriptomic and proteomic data sets. Many recent investigations have relied heavily on the use of the chromosome-contiguous genome of MHco3(ISE).N1 in the absence of a genome for Haecon-5. However, there has been no genetic comparison of these and other strains to date. Here, we assembled and characterised the mitochondrial genome (14.1 kb) of Haecon-5 and compared it with that of MHco3(ISE).N1 and two other strains (i.e., McMaster and NZ_Hco_NP) from Australasia. We detected 276 synonymous and 25 non-synonymous single nucleotide polymorphisms (SNPs) within Haecon-5. Between the Haecon-5 and MHco3(ISE).N1 strains, we recorded 345 SNPs, 31 of which were non-synonymous and linked to fixed amino acid differences in seven protein-coding genes (nad5, nad6, nad1, atp6, nad2, cytb and nad4) between these strains. Pronounced variation (344 and 435 SNPs) was seen between Haecon-5 and each of the other two strains from Australasia. The question remains as to what impact these mitogenomic mutations might have on the biology and physiology of H. contortus, which warrants exploration. The high degree of mitogenomic variability recorded here among these strains suggests that further work should be undertaken to assess the nature and extent of the nuclear genomic variation within H. contortus. [ABSTRACT FROM AUTHOR]

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host–parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin—with possible roles in modulating host immune responses and facilitating parasite survival—were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella–host interactions might offer possible avenues for developing new interventions against trichinellosis. [ABSTRACT FROM AUTHOR]

BackgroundThe barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites.ResultsThe draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules.ConclusionsThe draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders.

Parasitic trematodes (flukes) cause substantial mortality and morbidity in humans. The Chinese liver fluke, Clonorchis sinensis, is one of the most destructive parasitic worms in humans in China, Vietnam, Korea and the Russian Far East. Although C. sinensis infection can be controlled relatively well using anthelmintics, the worm is carcinogenic, inducing cholangiocarcinoma and causing major suffering in ~ 15 million people in Asia. This chapter provides an account of C. sinensis and clonorchiasis research--covering aspects of biology, epidemiology, pathogenesis and immunity, diagnosis, treatment and control, genetics and genomics. It also describes progress in the area of molecular biology (genetics, genomics, transcriptomics and proteomics) and highlights challenges associated with comparative genomics and population genetics. It then reviews recent advances in the sequencing and characterisation of the mitochondrial and nuclear genomes for a Korean isolate of C. sinensis and summarises salient comparative genomic work and the implications thereof. The chapter concludes by considering how advances in genomic and informatics will enable research on the genetics of C. sinensis and related parasites, as well as the discovery of new fluke-specific intervention targets. [ABSTRACT FROM AUTHOR]

Apicomplexan haemoparasites generate significant morbidity and mortality in humans and other animals, particularly in many low‐to‐middle income countries. Malaria caused by Plasmodium remains responsible for some of the highest numbers of annual deaths of any human pathogen, whilst piroplasmids, such as Babesia and Theileria can have immense negative economic effects through livestock loss. Diagnosing haemoparasites via traditional methods like microscopy is challenging due to low‐level and transient parasitaemia. PCR‐based diagnostics overcome these limitations by being both highly sensitive and specific, but they may be unable to accurately detect coinfections or identify novel species. In contrast, next‐generation sequencing (NGS)‐based methods can characterize all pathogens from a group of interest concurrently, although, the short‐read platforms previously used have been limited in the taxonomic resolution achievable. Here, we used Oxford Nanopore Technologies' (ONT) long‐read MinION™ sequencer to conduct apicomplexan haemoparasite metabarcoding via sequencing the near full‐length 18S ribosomal RNA gene, demonstrating its ability to detect Babesia, Hepatozoon, Neospora, Plasmodium, Theileria and Toxoplasma species. This method was tested on blood‐extracted DNA from 100 dogs and the results benchmarked against qPCR and Illumina‐based metabarcoding. For two common haemoparasites, nanopore sequencing performed as well as qPCR (kappa agreement statistics > 0.98), whilst also detecting one pathogen, Hepatozoon felis, missed by the other techniques. The long‐reads obtained by nanopore sequencing provide an improved species‐level taxonomic resolution whilst the method's broad applicability mean it can be used to explore apicomplexan communities from diverse mammalian hosts, on a portable sequencer that easily permits adaptation to field use. [ABSTRACT FROM AUTHOR]

The identification and characterization of essential genes are central to our understanding of the core biological functions in eukaryotic organisms, and has important implications for the treatment of diseases caused by, for example, cancers and pathogens. Given the major constraints in testing the functions of genes of many organisms in the laboratory, due to the absence of in vitro cultures and/or gene perturbation assays for most metazoan species, there has been a need to develop in silico tools for the accurate prediction or inference of essential genes to underpin systems biological investigations. Major advances in machine learning approaches provide unprecedented opportunities to overcome these limitations and accelerate the discovery of essential genes on a genome-wide scale. Here, we developed and evaluated a large language model- and graph neural network (LLM–GNN)-based approach, called 'Bingo', to predict essential protein-coding genes in the metazoan model organisms Caenorhabditis elegans and Drosophila melanogaster as well as in Mus musculus and Homo sapiens (a HepG2 cell line) by integrating LLM and GNNs with adversarial training. Bingo predicts essential genes under two 'zero-shot' scenarios with transfer learning, showing promise to compensate for a lack of high-quality genomic and proteomic data for non-model organisms. In addition, the attention mechanisms and GNNExplainer were employed to manifest the functional sites and structural domain with most contribution to essentiality. In conclusion, Bingo provides the prospect of being able to accurately infer the essential genes of little- or under-studied organisms of interest, and provides a biological explanation for gene essentiality. [ABSTRACT FROM AUTHOR]