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The mammalian imprinted Dlk1-Dio3 domain contains multiple lncRNAs, mRNAs, the largest miRNA cluster in the genome and four differentially methylated regions (DMRs), and deletion of maternally expressed RNA within this locus results in embryonic lethality, but the mechanism by which this occurs is not clear. Here, we optimized the model of maternally expressed RNAs transcription termination in the domain and found that the cause of embryonic death was apoptosis in the embryo, particularly in the liver. We generated a mouse model of maternally expressed RNAs silencing in the Dlk1-Dio3 domain by inserting a 3 × polyA termination sequence into the Gtl2 locus. By analyzing RNA-seq data of mouse embryos combined with histological analysis, we found that silencing of maternally expressed RNAs in the domain activated apoptosis, causing vascular rupture of the fetal liver, resulting in hemorrhage and injury. Mechanistically, termination of Gtl2 transcription results in the silencing of maternally expressed RNAs and activation of paternally expressed genes in the interval, and it is the gene itself rather than the IG-DMR and Gtl2-DMR that causes the aforementioned phenotypes. In conclusion, these findings illuminate a novel mechanism by which the silencing of maternally expressed RNAs within Dlk1-Dio3 domain leads to hepatic hemorrhage and embryonic death through the activation of apoptosis. [ABSTRACT FROM AUTHOR]

The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. Here we compare PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrate different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we perform CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We find that 20.6% of brain cells have at least one Mb-scale CNV, with some supported by bulk sequencing or single-cells from other brain regions. Our study highlights the importance of selecting whole genome amplification method and reference genome for CNV calling, while supporting the existence of somatic CNVs in healthy and diseased human brain. Comparison of single cell whole genome amplification methods using human brain nuclei determines suitability for detection of large somatic copy number variants by low coverage whole genome sequencing aligned to different reference genome versions. [ABSTRACT FROM AUTHOR]

ABSTRACT Eukaryotic genomes harbour sequences derived from non‐retroviral RNA viruses, known as endogenous viral elements (EVEs) or non‐retroviral integrated RNA virus sequences (NIRVS). These sequences represent a record of past infections and have been implicated in host anti‐viral response. We have created a program to identify viral sequences integrated in a host genome. It begins with a specimen BAM file and outputs candidate NIRVS, along with putative host insertion sites and overlapping genomic features of the host genome in XML and visual formats, with minimal intermediary intervention. We ran through this software short‐read data derived from the genomes of 222 wild‐caught A. aegypti mosquitoes, from a dozen geographical regions, and located putative NIRVS from seven virus families. This program is as accurate as currently available software for NIRVS detection, and represents a significant improvement in adaptability and user‐friendliness. Furthermore, the flexibility of this pipeline allows the user to search for sequence integrations across the genome of any organism, as long as a query sequence database and a reference genome is provided. Potential extended applications include identification of integrated transgenic sequences used for research or vector control strategies. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicinal plant Fallopia multiflora (hereafter AYY) is well known for its anti-hyperlipidaemia, immunomodulating, and hepatoprotective effects, attributed to its abundance of anthraquinones and stilbene glycosides, which are distinct to its variety F. multiflora var. angulata (hereafter CYY) in proportion and composition. In this study, telomere-to-telomere (T2T) genomes were assembled for AYY and CYY using PacBio HiFi reads and Hi-C data. The genome sizes, percentages of repetitive sequences, and numbers of protein-coding genes of AYY and CYY assemblies were 1,458.37 Mb/70.48%/84,768 and 1,174.38 Mb/67.36%/69,100, respectively. Comprehensive assessments confirmed high continuity (contig N50: 112.58 Mb and 94.83 Mb; number of gaps: 9 and 5), completeness (BUSCOs: 97.30% and 97.60%; LAI: 16.93 and 16.77), and correctness (QV: 51.42 and 52.60) of AYY and CYY assemblies. These T2T genomes of F. multiflora provide valuable resources for studying the biosynthesis of specialized metabolites and facilitating precise genetic improvement. [ABSTRACT FROM AUTHOR]

Despite showing the greatest primate diversity on the planet, genomic studies on Amazonian primates show very little representation in the literature. With 48 geolocalized high coverage whole genomes from wild uakari monkeys, we present the first population-level study on platyrrhines using whole genome data. In a very restricted range of the Amazon rainforest, eight uakari species (Cacajao genus) have been described and categorized into the bald and black uakari groups, based on phenotypic and ecological differences. Despite a slight habitat overlap, we show that posterior to their split 0.92 Mya, bald and black uakaris have remained independent, without gene flow. Nowadays, these two groups present distinct genetic diversity and group-specific variation linked to pathogens. We propose differing hydrology patterns and effectiveness of geographic barriers have modulated the intra-group connectivity and structure of bald and black uakari populations. With this work we have explored the effects of the Amazon rainforest's dynamism on wild primates' genetics and increased the representation of platyrrhine genomes, thus opening the door to future research on the complexity and diversity of primate genomics. Population study of whole genomes of wild uakary monkeys (Cacajao genus) exposes how the dynamic and highly heterogeneous Amazon basin may have shaped complex connectivity patterns and driven fast population differentiation on these. [ABSTRACT FROM AUTHOR]

Robbsia andropogonis is one of the most destructive leaf spot disease pathogens of numerous host plants and causes heavy economic damage. In the present study, the complete genome of R. andropogonis strain BLB1, causing the leaf spot disease of areca palm, was generated using a hybrid method combining ONT PromethION long reads and BGISEQ-500 short reads. The resulting genome consists of seven replicons totaling 6,828,120 bp, and 5,808 genes were annotated, including 788 virulence-related genes. Function analysis showed that genes involved in metabolism were the most abundant group. Impressively, the bacteria were well-equipped with four, two, and four sets of type three, four, and six secretion systems, respectively, highlighting the virulence features of R. andropogonis BLB1. As the first complete genome sequence of the species of genus Robbsia, the BLB1 genome provides a solid foundation for investigation of mechanisms underlying the pathogen virulence and disease control, and will promote further discovery and characterization of the genus Robbsia. [ABSTRACT FROM AUTHOR]

The family Erinaceidae encompasses 27 extant species in two subfamilies: Erinaceinae, which includes spiny hedgehogs, and Galericinae, which comprises silky‐furred gymnures and moonrats. Although they are commonly recognized by the general public, their phylogenetic history remains incompletely understood, and several species have never been included in any molecular analyses. Additionally, previous research suggested that the species diversity of Erinaceidae might be underestimated. In this study, we sequenced the mitochondrial genomes of 29 individuals representing 18 erinaceid species using 18 freshly collected tissue and 11 historical museum specimens. We also integrated previously published data for a concatenated analysis. We aimed to elucidate the evolutionary relationships within Erinaceidae, estimate divergence times, and uncover potential underestimated species diversity. Our data finely resolved intergeneric and interspecific relationships and presented the first molecular evidence for the phylogenetic position of Mesechinus wangi, Paraechinus micropus, and P. nudiventris. Our results revealed a sister relationship between Neotetracus and Neohylomys gymnures, as well as a sister relationship between Hemiechinus and Mesechinus, supporting previous hypotheses. Additionally, our findings provided a novel phylogenetic position for Paraechinus aethiopicus, placing it in a basal position within the genus. Furthermore, our study uncovered cryptic species diversity within Hylomys suillus as well as in Neotetracus sinensis, Atelerix albiventris, P. aethiopicus, and Hemiechinus auratus, most of which have been previously overlooked. [ABSTRACT FROM AUTHOR]

The Xerces Blue (Glaucopsyche xerces) is considered to be the first butterfly to become extinct in historical times. It was notable for its chalky lavender wings with conspicuous white spots on the ventral wings. The last individuals were collected in their restricted habitat, in the dunes near the Presidio military base in San Francisco, in 1941. We sequenced the genomes of four 80- to 100-year-old Xerces Blue, and seven historical and one modern specimens of its closest relative, the Silvery Blue (Glaucopsyche lygdamus). We compared these to a novel annotated genome of the Green-Underside Blue (Glaucopsyche alexis). Phylogenetic relationships inferred from complete mitochondrial genomes indicate that Xerces Blue was a distinct species that diverged from the Silvery Blue lineage at least 850,000 years ago. Using nuclear genomes, both species experienced population growth during the Eemian interglacial period, but the Xerces Blue decreased to a very low effective population size subsequently, a trend opposite to that observed in the Silvery Blue. Runs of homozygosity and deleterious load in the former were significantly greater than in the later, suggesting a higher incidence of inbreeding. These signals of population decline observed in Xerces Blue could be used to identify and monitor other insects threatened by human activities, whose extinction patterns are still not well known. [ABSTRACT FROM AUTHOR]

The original methodology for describing the pangenome of a prokaryotic species is based on modeling genomes as unordered sets of genes. More recent findings have underlined the importance of considering the ordering of genes along the genetic material as well, when making comparisons among genomes. To further investigate the benefits of gene order when describing genomes of a given species, we applied two distance metrics on a dataset of 84 genomes of Staphylococcus epidermidis. The first metric, GeLev, depends on the order of genes and is a derivative of the Levenshtein distance. The second, the Jaccard distance, depends on gene sets only. The application of these distances reveals information about the global structure of the genomes, and allows clustering of the genomes into classes. The main biological result is that, while genomes within the same class are structurally similar, genomes of different classes have an additional characteristic. Between genomes in different classes we can discover instances where a large segment of the first genome appears in reverse order in the second. This feature suggests that genome rearrangements in S. epidermidis happen on a large scale, while micro-rearrangements of single or a small number of genes are rare. Thus, this paper describes a straight-forward method to classify genomes into structural classes with the same order of genes and makes it possible to visualize reversed segments in pairs of genomes. The method can be readily applied to other species. [ABSTRACT FROM AUTHOR]

Whole genome sequencing has been an effective tool in the discovery of variants that cause rare diseases. In this study, we determined the suitability of a novel avidity sequencing approach for rare disease applications. We built a sample to results workflow, combining this sequencing technology with standard library preparation kits, analysis workflows, and interpretation tools. We applied the workflow to ten pedigrees with inherited retinal degeneration (IRD) phenotype. Candidate variants of interest identified through whole genome sequencing were further evaluated using segregation analysis in the additional family members. Potentially causal variants in known IRD genes were detected in five of the ten cases. These high confidence variants were found in ABCA4, CERKL, MAK, PEX6 and RDH12 genes associated with retinal degeneration, that could be sufficient to cause pathology. Pending confirmatory clinical evaluation, we observed a 50% diagnostic yield, consistent with previously reported outcomes of IRD patient analysis. The study confirms that avidity sequencing is effective in detection of causal variants when used for whole genome sequencing in rare disease applications. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Uveal melanoma (UM) can be classified by tumour size category and by The Cancer Genome Atlas (TCGA) groups (cytogenetic‐based, 4‐category prognostic classification into Groups A‐D). This study was conducted to assess impact on metastasis‐free survival (MFS) in UM by tumour size category based on correlation with TCGA classification.Retrospective analysis of 1001 cases categorised as small (0.0–3.0 mm), medium (3.1–8.0 mm) and large (≥8.1 mm), grouped by TCGA classification.Of 1001 cases, TCGA Groups (A/B/C/D) included small (n = 270, 75%/11%/13%/1%), medium (n = 503, 46%/14%/27%/13%) and large (n = 228, 23%/19%/38%/20%) UM. The 5‐and 10‐year Kaplan–Meier MFS for small UM revealed Group A (98%, 98%), Group B (100%, 100%), Group C (86%, NA) and Group D (100%, NA). For medium UM, the values dropped with Group A (95%, 93%), Group B (90%, 90%), Group C (68%, 38%), and Group D (44%, NA). For large UM, the values dropped further with Group A (94%, 86%), Group B (85%, NA), Group C (40%, 28%), and Group D (23%, NA). Additionally, a comparison (small vs. medium vs. large tumour size category) revealed TCGA low‐risk grouping (Groups A or B) in 86% vs. 60% vs. 58% cases with UM.By tumour size category, favourable cytogenetics (Groups A or B) is found in 86% of small tumours, 60% of medium tumours, and 58% of large tumours. The MFS at 10 years for favourable cytogenetics was 98% for small tumours, 92% for medium tumours, and 54% for large tumours. Tumour size category can serve as a surrogate for TCGA. [ABSTRACT FROM AUTHOR]

Dolichandrone spathacea is a mangrove associate with high medicinal and ecological values. However, due to the dual-pressure of climate change and human activities, D. spathacea has become endangered in China. Moreover, misidentification between D. spathacea and its terrestrial relative D. cauda-felina poses further challenges to field protection and proper medicinal usage of D. spathacea. Thus, to address these problems, we sequenced and assembled mitochondrial (mt) and chloroplast (cp) genomes for both D. spathacea and D. cauda-felina. Comparative analysis revealed apparently different size and scaffold number between the two mt genomes, but a high similarity between the cp genomes. Eight regions with high sequence divergence were identified between the two cp genomes, which might be used for developing candidate DNA markers for distinguishing the two species. The splitting between D. spathacea and D. cauda-felina was inferred to occur at ~6.8 - 7.7 million years ago (Mya), which may be driven by the environment fluctuations in late Miocene. In the cp genome, 12 genes related to the expression of photosynthesis-associated proteins were detected with signatures of positive selection, which may contribute to the origin and evolutionary adaptation of Dolichandrone mangrove species. These new findings do not only enrich organelle genomic resources of Dolichandrone species, but also provide important genetic clues for improving the conservation and proper usage of endangered mangrove associate D. spathacea. [ABSTRACT FROM AUTHOR]

Genetic markers play a central role in understanding genetic diversity, speciation, evolutionary processes, and how species respond to environmental stresses. However, conventional molecular markers are less effective when studying polyploid species with large genomes. In this study, we compared gene expression levels in 101 accessions of Elymus sibiricus, a widely distributed allotetraploid forage species across the Eurasian continent. A total of 20,273 high quality transcriptomic SNPs were identified. In addition, 72,344 evolutionary information loci of these accessions of E. sibiricus were identified using genome skimming data in conjunction with the assembled composite genome. The population structure results suggest that transcriptome SNPs were more effective than SNPs derived from genome skimming data in revealing the population structure of E. sibiricus from different locations, and also outperformed gene expression levels. Compared with transcriptome SNPs, the investigation of population-specifically-expressed genes (PSEGs) using expression levels revealed a larger number of locally adapted genes mainly involved in the ion response process in the Sichuan, Inner Mongolia, and Xizang geographical groups. Furthermore, we performed the weighted gene co-expression network analysis (WGCNA) and successfully identified potential regulators of PSEGs. Therefore, for species lacking genomic information, the use of transcriptome SNPs is an efficient approach to perform population structure analysis. In addition, analyzing genes under selection through nucleotide diversity and genetic differentiation index analysis based on transcriptome SNPs, and exploring PSEG through expression levels is an effective method for analyzing locally adaptive genes. [ABSTRACT FROM AUTHOR]

Break-induced replication (BIR) is mutagenic, and thus its use requires tight regulation, yet the underlying mechanisms remain elusive. Here we uncover an important role of 53BP1 in suppressing BIR after end resection at double strand breaks (DSBs), distinct from its end protection activity, providing insight into the mechanisms governing BIR regulation and DSB repair pathway selection. We demonstrate that loss of 53BP1 induces BIR-like hyperrecombination, in a manner dependent on Polα-primase-mediated end fill-in DNA synthesis on single-stranded DNA (ssDNA) overhangs at DSBs, leading to PCNA ubiquitination and PIF1 recruitment to activate BIR. On broken replication forks, where BIR is required for repairing single-ended DSBs (seDSBs), SMARCAD1 displaces 53BP1 to facilitate the localization of ubiquitinated PCNA and PIF1 to DSBs for BIR activation. Hyper BIR associated with 53BP1 deficiency manifests template switching and large deletions, underscoring another aspect of 53BP1 in suppressing genome instability. The synthetic lethal interaction between the 53BP1 and BIR pathways provides opportunities for targeted cancer treatment. Break-induced replication (BIR) mechanism is mutagenic, and thus needs to be tightly regulated. Here the authors identify an important role of 53BP1 in suppressing mutagenic BIR, providing insights into DSB repair pathway selection and BIR regulation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the genetic causes of 22 patients with clinically high suspicion of X‐linked hypohidrotic ectodermal dysplasia from 20 unrelated Chinese families, expand the spectrum of ectodysplasin‐A mutations, and provide more evidence for variants of uncertain significance. Subjects and Methods: Whole‐exome sequencing was performed and potentially pathogenic variants were verified by Sanger sequencing. Western blotting, real‐time PCR and immunofluorescence analyses were performed to investigate the preliminary functions of the candidate variants. Results: Nineteen ectodysplasin‐A variants were identified, six of which were not previously reported. Among these variants, we identified a patient who carried two mutations in ectodysplasin‐A and exhibited more severe phenotypes. Additionally, mutant protein expression levels decreased, whereas mRNA transcription levels increased. Cellular sublocalisation of the variants located in the tumour necrosis factor homologous domain showed that the proteins accumulated in the nucleus, whereas wild‐type proteins remained in the cell membrane. A rare indel variant and two classical splicing variants that lead to exon 7 skipping were detected. Conclusions: This study provides definitive diagnoses for 20 families with suspected X‐linked hypohidrotic ectodermal dysplasia and additional information on clinical heterogeneity and genotype–phenotype relationships. [ABSTRACT FROM AUTHOR]

ABSTRACT Light is a vital environmental signal that regulates the expression of plastid genes. Plastids are crucial organelles that respond to light, but the effects of light on plastid RNA processing following transcription remain unclear. In this study, we systematically examined the influence of light exposure on plastid RNA processing, focusing on RNA splicing and RNA editing. We demonstrated that light promotes the splicing of transcripts from the plastid genes rps12, ndhA, atpF, petB, and rpl2. Additionally, light increased the editing rate of the accD transcript at nucleotide 794 (accD‐794) and the ndhF transcript at nucleotide 290 (ndhF‐290), while decreasing the editing rate of the clpP transcript at nucleotide 559 (clpP‐559). We have identified key regulators of signaling pathways, such as CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), ELONGATED HYPOCOTYL 5 (HY5), and PHYTOCHROME‐INTERACTING FACTORs (PIFs), as important players in the regulation of plastid RNA splicing and editing. Notably, COP1 was required for GENOMES UNCOUPLED1 (GUN1)‐dependent repression of clpP‐559 editing in the light. We showed that HY5 and PIF1 bind to the promoters of nuclear genes encoding plastid‐localized RNA processing factors in a light‐dependent manner. This study provides insight into the mechanisms underlying light‐mediated post‐transcriptional regulation of plastid gene expression. [ABSTRACT FROM AUTHOR]

Complex pathways involving the DNA damage response (DDR) contend with cell-intrinsic and -extrinsic sources of DNA damage. DDR mis-regulation results in genome instability that can contribute to aging and diseases including cancer and neurodegeneration. Recent studies have highlighted key roles for several RNA species in the DDR, including short RNAs and RNA/DNA hybrids (R-loops) at DNA break sites, all contributing to efficient DNA repair. RNAs can undergo more than 170 distinct chemical modifications. These RNA modifications have emerged as key orchestrators of the DDR. Here, we highlight the function of enzyme- and non-enzyme-induced RNA modifications in the DDR, with particular emphasis on m6A, m5C, and RNA editing. We also discuss stress-induced RNA damage, including RNA alkylation/oxidation, RNA-protein crosslinks, and UV-induced RNA damage. Uncovering molecular mechanisms that underpin the contribution of RNA modifications to DDR and genome stability will have direct application to disease and approaches for therapeutic intervention. Xhemalçe et al. review emerging roles of RNA modifications in DNA damage responses. Chemical alterations to RNA, including m6A, m5C, and RNA editing, play active roles in repairing DNA damage. RNA damage also occurs, which triggers stress responses. These pathways promote mechanisms critical for genome integrity and cellular homeostasis. [ABSTRACT FROM AUTHOR]

Mammalian genomes produce an abundance of short RNA. This is, to a large extent, due to the genome-wide and spurious activity of RNA polymerase II (RNAPII). However, it is also because the vast majority of initiating RNAPII, regardless of the transcribed DNA unit, terminates within a ∼3-kb early "pausing zone." Given that the resultant RNAs constitute both functional and non-functional species, their proper sorting is critical. One way to think about such quality control (QC) is that transcripts, from their first emergence, are relentlessly targeted by decay factors, which may only be avoided by engaging protective processing pathways. In a molecular materialization of this concept, recent progress has found that both "destructive" and "productive" RNA effectors assemble at the 5′ end of capped RNA, orchestrated by the essential arsenite resistance protein 2 (ARS2) protein. Based on this principle, we here discuss early QC mechanisms and how these might sort short RNAs to their final fates. [Display omitted] The majority of initiating RNA polymerase II (RNAPII) terminates early, generating an abundance of short RNAs that require sorting into productive or destructive pathways. Here, Garland and Jensen explore early quality-control mechanisms that govern the fate of short RNAs, preventing the accumulation of non-functional transcripts and ensuring proper RNA processing. [ABSTRACT FROM AUTHOR]

Background: Cladocopium infistulum (Symbiodiniaceae) is a dinoflagellate specialized to live in symbiosis with western Pacific giant clams (Tridacnidae). Unlike coral-associated symbionts, which reside within the host cells, C. infistulum inhabits the extracellular spaces of the clam's digestive diverticula. It is phylogenetically basal to a large species complex of stress-tolerant Cladocopium, many of which are associated with important reef-building corals in the genus Porites. This close phylogenetic relationship may explain why C. infistulum exhibits high thermotolerance relative to other tridacnid symbionts. Moreover, past analyses of microsatellite loci indicated that Cladocopium underwent whole-genome duplication prior to the adaptive radiations that led to its present diversity. Results: A draft genome assembly of C. infistulum was produced using long- and short-read sequences to explore the genomic basis for adaptations underlying thermotolerance and extracellular symbiosis among dinoflagellates and to look for evidence of genome duplication. Comparison to three other Cladocopium genomes revealed no obvious over-representation of gene groups or families whose functions would be important for maintaining C. infistulum's unique physiological and ecological properties. Preliminary analyses support the existence of partial or whole-genome duplication among Cladocopium, but additional high-quality genomes are required to substantiate these findings. Conclusion: Although this investigation of Cladocopium infistulum revealed no patterns diagnostic of heat tolerance or extracellular symbiosis in terms of overrepresentation of gene functions or genes under selection, it provided a valuable genomic resource for comparative analyses. It also indicates that ecological divergence among Cladocopium species, and potentially among other dinoflagellates, is partially governed by mechanisms other than gene content. Thus, additional high-quality, multiomic data are needed to explore the molecular basis of key phenotypes among symbiotic microalgae. [ABSTRACT FROM AUTHOR]

Xylophilus ampelinus is a xylematic bacterium causing bacterial blight of grapevine, a disease regarded as a potential threat for viticulture in several countries. Currently, PCR detection is pivotal in diagnostic protocols due to the bacterium's infrequent occurrence in the field and the technical advantages of PCR. Recent metagenomic studies have unveiled diversity in its taxonomic domain, unknown when the most widely used assays for the detection of X. ampelinus infections were developed. In particular, PCR assays relying on highly conserved sequence regions, such as those surrounding ribosomal RNA genes, may be substituted with more specific PCR assays. In this study, we first investigated the diversity of detectable grapevine endophytes related to but different from X. ampelinus and delineated the genotaxonomic boundaries of the species in relation to the known (meta)genomes of closely related bacteria. Then, by exploiting the wealth of genomes now available for bacteria classified in the Burkholderiales, we devised several sets of primers targeting only X. ampelinus and its closest relatives. These primers were employed to (i) genotaxonomically circumscribe the grapevine endophyte species related to but distinguishable from X. ampelinus and (ii) develop a robust multiplex PCR assay expected to be specific for the species X. ampelinus based on in vitro and in silico evidence. The adoption of the multiplex PCR assay presented here is expected to reduce the risk of false positives in the diagnosis of bacterial blight of grapevine. [ABSTRACT FROM AUTHOR]

We identified a novel human circovirus in an immunocompromised 66-year-old woman with sudden onset of self-limiting hepatitis. We detected human circovirus 1 (HCirV-1) transcripts in hepatocytes and the HCirV-1 genome long-term in the patient’s blood, stool, and urine. HCirV-1 is an emerging human pathogen that persists in susceptible patients. [ABSTRACT FROM AUTHOR]

Topologically associating domain (TAD) boundaries are the flanking edges of TADs, also known as insulated neighborhoods, within the 3D structure of genomes. A prominent feature of TAD boundaries in mammalian genomes is the enrichment of clustered CTCF sites often with mixed orientations, which can either block or facilitate enhancer–promoter (E‐P) interactions within or across distinct TADs, respectively. We will discuss recent progress in the understanding of fundamental organizing principles of the clustered CTCF insulator codes at TAD boundaries. Specifically, both inward‐ and outward‐oriented CTCF sites function as topological chromatin insulators by asymmetrically blocking improper TAD‐boundary‐crossing cohesin loop extrusion. In addition, boundary stacking and enhancer clustering facilitate long‐distance E‐P interactions across multiple TADs. Finally, we provide a unified mechanism for RNA‐mediated TAD boundary function via R‐loop formation for both insulation and facilitation. This mechanism of TAD boundary formation and insulation has interesting implications not only on how the 3D genome folds in the Euclidean nuclear space but also on how the specificity of E‐P interactions is developmentally regulated. [ABSTRACT FROM AUTHOR]

Repetitive DNA sequences cause genomic instability and are important genetic markers. Identification of repeats is a critical step in genome annotation and analysis. On the other hand, repeats also pose a technical challenge for genome assembly and alignment programs using NGS data. RFGR is a comprehensive tool that can find exact repetitive sequences in complete genomes and assembled genomes, as well as NGS reads of prokaryotes. For complete genomes, RFGR uses a suffix trees to find seed repeats of repetitive sequences of fixed length with indels. For assembled genomes, RFGR uses a modified Bowtie aligner to find seed repeats of exact repetitive sequences in the contigs/ scaffolds, which are then extended to maximal repeats. The repeats are classified and for repeats near a gene, RFGR reports the gene as well. For the control dataset of E. coli UTI89 and E. coli K12, RFGR reports 35,141 and 49,352 repeats, respectively. For NGS reads, RFGR uses the frequency of the repetitive k-mers to determine FASTQ reads containing repetitive sequences and removes them from the dataset. An E. coli K12 NGS dataset pre-processed using RFGR, on comparison with the original dataset, gives an improved assembly. The N50 value improves by 22.86% with a decrease in size of the assembly graph by nearly 50%. Thus, with RFGR, we achieve a better assembly with reduced computation. RFGR can be improved in terms of the length of the minimum repeat found, extending to find approximate repeats and to be applicable to Eukaryotes as well. [ABSTRACT FROM AUTHOR]

Five Phyllanthus species were characterized using a fluorochrome chromosome banding technique with CMA and DAPI. This genus displayed a range of somatic chromosomal counts, including 2n = 2x = 26 (diploid) in P. acidus, P. niruri, and P. reticulatus; 2n = 6x = 48 (hexaploid) in P. urinaria; and 2n = 10x = 100 (decaploid) in P. emblica (wild and cultivated varieties), which exhibited a multi-basic chromosome number. The centromeric and terminal regions of the chromosomes contained most of the CMA and DAPI bands, indicating that GC- and AT-rich repeats had accumulated in these locations. The diversity based on the heterochromatin distribution patterns made it possible to use the CMA and DAPI banding approaches to analyze and characterize these five Phyllanthus species. [ABSTRACT FROM AUTHOR]

Purpose: Postpartum depression (PPD) brings adverse and serious consequences to both new parents and newborns. Neuroticism affects PPD, which remains controversial for confounding factors and reverse causality in cross-sectional research. Therefore, mendelian randomization (MR) study has been adopted to investigate their causal relationship. Methods: This study utilized large-scale genome-wide association study genetic pooled data from three major databases: the United Kingdom Biobank, the European Bioinformatics Institute, and the FinnGen databases. The causal analysis methods used inverse variance weighting (IVW). The weighted median, MR-Egger method, MR-PRESSO test, and the leave-one-out sensitivity test have been used to examine the results' robustness, heterogeneity, and horizontal pleiotropy. The fixed effect model yielded the results of meta-analysis. Results: In the IVW model, a meta-analysis of the MR study showed that neuroticism increased the risk of PPD (OR, 1.17; 95% CI, 1.11–1.25, p < 0.01). Reverse analysis showed that PPD could not genetically predict neuroticism. There was no significant heterogeneity or horizontal pleiotropy bias in this result. Conclusion: Our study suggests neuroticism is the risk factor for PPD from a gene perspective and PPD is not the risk factor for neuroticism. This finding may provide new insights into prevention and intervention strategies for PPD according to early detection of neuroticism. [ABSTRACT FROM AUTHOR]

Summary: The genomes of ectomycorrhizal (ECM) fungi have a reduced number of genes encoding Carbohydrate‐Active EnZymes (CAZymes), expansions in transposable elements (TEs) and small secreted proteins (SSPs) compared with saprotrophs. Fewer genes for specific peptidases and lipases in ECM fungi are also reported. It is unclear whether these changes occur at the shift to the ECM habit or are more gradual throughout the evolution of ECM lineages.We generated a genomic dataset of 20 species in the ECM lineage Inocybaceae and compared them with six saprotrophic species.Inocybaceae genomes have fewer CAZymes, peptidases, lipases, secondary metabolite clusters and SSPs and higher TE content than their saprotrophic relatives. There was an increase in the rate of gene family evolution along the branch with the transition to the ECM lifestyle. This branch had very high rate of evolution in CAZymes and had the largest number of contractions. Other significant changes along this branch included expansions in transporters, transposons‐related genes and communication genes such as fungal kinases.There is a high concentration of changes in proximity to the transition to the ECM lifestyle, which correspond to the identified key changes for the gain of this lifestyle. [ABSTRACT FROM AUTHOR]

The family Rhabdoviridae includes viruses with a negative-sense RNA genome. This family is divided into four subfamilies, and until recently, the subfamily Betarhabdovirinae, encompassing all plant-associated rhabdoviruses, was further divided into six genera. Here, we report the creation of two new genera within the subfamily Betarhabdovirinae – Alphagymnorhavirus and Betagymnorhavirus – to include recently described gymnosperm-associated viruses. The genus Alphagymnorhavirus includes nine species, while the genus Betagymnorhavirus includes only one species. Phylogenetic analysis indicated that these viruses form two well-supported clades that are clustered with the varicosaviruses, which have bisegmented genomes. In contrast, the 10 viruses included in the newly created genera have the distinctive feature that they have an unsegmented genome encoding five or six proteins. The creation of the genera Alphagymnorhavirus and Betagymnorhavirus has been ratified by the International Committee on Taxonomy of Viruses (ICTV). [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify, discover and explore the characteristics of the mtDNA genomes of Cemani chicken (Gallus gallus). Methods: This study used gDNA of Cemani chicken isolated from liver tissue. mtDNA sequencing was performed using WGS mtDNA analysis with nanopore technology by Oxford Nanopore Technologies GridION. Bioinformatics and data analysis were then performed. Results: This study showed that the length of the mtDNA genome is 16,789 bp, consisting of two ribosomal RNA (12S rRNA, 16S rRNA), 22 transfer RNA genes (trnR, trnG, trnK, trnD, trnS, trnY, trnC, trnN, trnA, trnW, trnM, trnQ, trnl, trnL, trnV, trnF, trnP, trnT, trnE, trnL, trnS, trnH), 13 protein-coding genes (PCGs) (ND4l, ND3, COX3, ATP6, ATP8, COX2, COX1, ND2, ND1, CYTB, ND6, ND5, ND4), and a noncoding control region (Dloop). Furthermore, analysis showed there were polymorphic sites and amino acid alterations when mtDNA Cemani chicken was aligned with references from GenBank. Conclusion: Site (988T>*) in Dloop genes and (328A>G) in ND3 genes which alter glycine to stop codon, were specific markers found only in Cemani chicken. [ABSTRACT FROM AUTHOR]

Background: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients < 25 years of age. Through exome sequencing, identification of > 65 monogenic causes has revealed insights into disease mechanisms of nephrotic syndrome (NS). Methods: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with exome sequencing in a worldwide cohort of 1649 pediatric patients with NS. Results: We identified homozygous missense variants in MYO1C in two unrelated children with NS (c.292C > T, p.R98W; c.2273 A > T, p.K758M). We evaluated publicly available kidney single-cell RNA sequencing datasets and found MYO1C to be predominantly expressed in podocytes. We then performed structural modeling for the identified variants in PyMol using aligned shared regions from two available partial structures of MYO1C (4byf and 4r8g). In both structures, calmodulin, a common regulator of myosin activity, is shown to bind to the IQ motif. At both residue sites (K758; R98), there are ion-ion interactions stabilizing intradomain and ligand interactions: R98 binds to nearby D220 within the myosin motor domain and K758 binds to E14 on a calmodulin molecule. Variants of these charged residues to non-charged amino acids could ablate these ionic interactions, weakening protein structure and function establishing the impact of these variants. Conclusion: We here identified recessive variants in MYO1C as a potential novel cause of NS in children. [ABSTRACT FROM AUTHOR]

The Cape hare (Lepus capensis) is among the most widely distributed hare species globally, inhabiting extensive regions across Africa, the Middle East, and Central Asia. However, evolutionary and genetic research on L. capensis was seriously impeded by the absence of a reference genome. Here, we assembled and constructed a chromosome-level genome of L. capensis (with scaffolds anchored to 25 chromosomes and a total assembled length of 2.9 Gb, achieving a contig N50 length of 124.44 Mb) using PacBio HiFi sequencing and Hi-C assembly technology. Evaluation using BUSCO indicated the genome assembly to be 98.2% complete. The de novo prediction revealed that repetitive sequences constitute 46.13% of the entire genome, and long interspersed nuclear elements (LINEs) constituted the largest portion. We annotated a total of 13, 868 protein-coding genes using transcriptomes from two tissues (muscle and skin). This high-quality reference genome serves as a valuable genomic resource for advancing genetic studies in this species. [ABSTRACT FROM AUTHOR]

Although advances in long-read sequencing technology and genome assembly techniques have facilitated the study of genomes, little is known about the genomes of unique Chinese indigenous breeds, including the Huai pig. Huai pig is an ancient domestic pig breed and is well-documented for its redder meat color and high forage tolerance compared to European domestic pigs. In the present study, we sequenced and assembled the Huai pig genome using PacBio, Hi-C, and Illumina sequencing technologies. The final highly contiguous chromosome-level Huai pig genome spans 2.53 Gb with a scaffold N50 of 138.92 Mb. The Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness score for the assembled genome was 95.33%. Remarkably, 23,389 protein-coding genes were annotated in the Huai-pig genome, along with 45.87% repetitive sequences. Overall, this study provided new foundational resources for future genetic research on Chinese domestic pigs. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Haplotype-resolved chromosome-level genome assembly of Ehretia macrophylla" published in Scientific Data. The correction addresses errors in Figure 1b and Figure 3 of the article. In Figure 1b, the chromosome number for haplotype b was incorrectly given as chr21b instead of chr20b. In Figure 3, the vertical coordinates were labeled erroneously as chr01a, chr01b... to chr20a, chr20b, but the correct order should be from top to bottom: chr20b, followed by chr20a... to chr01b, and finally chr01a. The corrected versions of the figures are provided in the document. The authors of the article are Shiping Cheng, Qikun Zhang, Xining Geng, Lihua Xie, Minghui Chen, Siqian Jiao, Shuaizheng Qi, Pengqiang Yao, Mailin Lu, Mengren Zhang, Wenshan Zhai, Quanzheng Yun, and Shangguo Feng. [Extracted from the article]

Investigating plant genomes offers crucial foundational resources for exploring various aspects of plant biology and applications, such as functional genomics and breeding practices. With the development in sequencing and assembly technology, several Nicotiana tabacum genomes have been published. In this paper, we reviewed the progress on N. tabacum genome assembly and quality, from the initial draft genomes to the recent high-quality chromosome-level assemblies. The application of long-read sequencing, optical mapping, and Hi-C technologies has significantly improved the contiguity and completeness of N. tabacum genome assemblies, with the latest assemblies having a contig N50 size over 50 Mb. Despite these advancements, further improvements are still required and possible, particularly on the development of pan-genome and telomere-totelomere (T2T) genomes. These new genomes will capture the genomic diversity and variations among different N. tabacum cultivars and species, and provide a comprehensive view of the N. tabacum genome structure and gene content, so to deepen our understanding of the N. tabacum genome and facilitate precise breeding and functional genomics. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, coxsackievirus (CV) A10 has been associated with increasing sporadic hand, foot, and mouth disease (HFMD) cases and outbreaks globally. In addition to mild symptoms such as pharyngitis and herpangina, CVA10-related complications or even fatality can occur. Currently, systematic phylogenetic studies of CVA10 are limited. Methods: In this study, we first explored the epidemiological and genetic characteristics of CVA10 in Nanchang, an inland southeastern city of China, based on the HFMD surveillance network from 2015-2023. Results: Among 3429 enterovirus-positive cases, 110 (3.04%) were associated with CVA10, with a male-to-female ratio of 1.62. The median age of the CVA10 patients was 2.3 years (interquartile range, IQR 1.0-4.0), with 94.55% (104/110) of the patients aged less than 5 years. Phylogenetic analyses using the full-length VP1, 5'UTR, P1, P2, P3 sequences and near full-length genomes indicated that CVA10 strains (n = 57) isolated in Nanchang belonged to genogroup C; two strains identified in 2017 belonged to C1 subtypes clustered with strains from Vietnam, Madagascar, France and Spain; and the others belonged to C2 subtypes interdigitating with CVA10 isolates from mainland China, the United States and Australia. Through extensive analysis, we identified a rare F168Y mutation in epitope 4 of VP1 in a Madagascar strain of genogroup F and a Chinese strain of genogroup C. Based on Bayesian evolutionary analyses, the average nucleotide substitution rate for the VP1 gene of CV10 strains was 3.07×10-3 substitutions/site/year. The most recent common ancestor (tMRCA) of genogroup C was dated 1990.84, and the tMRCA of CVA10 strains from Nanchang was dated approximately 2003.16, similar to strains circulating in other regions of China, suggesting that the viruses were likely introduced and cryptically circulated in China before the establishment of the HFMD surveillance network. Recombination analysis indicated intertypic recombination of the Nanchang strain with the genogroup G strain in the 3D region. Discussion: Given the shifting dominance of viral genotypes and frequent recombination events, the existing surveillance system needs to be regulated to enhance genomic surveillance efforts on a more diverse spectrum of genotypes in the future. [ABSTRACT FROM AUTHOR]

Formaldehyde (FA) is a chemical that facilitates crosslinking between DNA and proteins. It is widely used in various biochemical assays, such as chromosome conformation capture (3C) and Chromatin Immunoprecipitation (ChIP). While the concentration and temperature of FA treatment are recognized as crucial factors in crosslinking, their quantitative effects have largely remained unexplored. In this study, we employed 3C as a model system to systematically assess the impacts of these two factors on crosslinking. Our findings indicate that the strength of crosslinking significantly influences chromatin conformation detection at nearly all known structural levels. Specifically, a delicate balance between sensitivity and reliability is required when detecting higher-level structures, such as chromosome compartments. Conversely, intense crosslinking is preferred when targeting lower-level structures, such as topologically associated domains (TADs) or chromatin loops. Based on our data, we propose a conceptual molecular thermal motion model to elucidate the roles of these two factors in restricting FA crosslinking. Our results not only shed light on the previously overlooked confounding factor in FA crosslinking but also highlight the need for caution in new technology developments that rely on FA crosslinking. This methodological study examines the effects of temperature and formaldehyde concentration on the analysis of genome organization by chromosome conformation capture approaches and reveals that changes in these two key parameters can greatly affect the outcome and reproducibility of the analysis. [ABSTRACT FROM AUTHOR]

Protogyny, being capable of changing from female to male during their lifetime, is prevalent in 20 families of teleosts but is believed to have evolved within specific evolutionary lineages. Therefore, shared regulatory factors governing the sex change process are expected to be conserved across protogynous fishes. However, a comprehensive understanding of this mechanism remains elusive. To identify these factors, we conducted a meta‐analysis using gonadal transcriptome data from seven species. We curated data pairs of ovarian tissue and transitional gonad, and employed ratios of expression level as a unified criterion for differential expression, enabling a meta‐analysis across species. Our approach revealed that classical sex change‐related genes exhibited differential expression levels between the ovary and transitional gonads, consistent with previous reports. These results validate our methodology's robustness. Additionally, we identified novel genes not previously linked to gonadal sex change in fish. Notably, changes in the expression levels of acetoacetyl‐CoA synthetase and apolipoprotein Eb, which are involved in cholesterol synthesis and transport, respectively, suggest that the levels of cholesterol, a precursor of steroid hormones crucial for sex change, are decreased upon sex change onset in the gonads. This implies a potential universal influence of cholesterol dynamics on gonadal transformation in protogyny. [ABSTRACT FROM AUTHOR]

Background: Although there is considerable evidence of a robust correlation between rheumatoid arthritis (RA) and carpal tunnel syndrome (CTS) in previous research, the causal link between the two remains a topic of controversy. Methods: We conducted a two-sample Mendelian randomization (MR) study to explore the causal impact of RA on CTS. We obtained aggregate data from genome-wide association studies (GWAS) of CTS (ebi database and GEO database) and RA (FinnGen database). This study employed five MR analysis methods, with a focus on the inverse variance-weighted (IVW) method. Sensitivity analyses were conducted to ensure the robustness of the results of this study. Additionally, we performed reverse MR analysis. Results: We selected 84 and 78 single nucleotide polymorphisms (SNPs) significantly associated with RA from two databases as instrumental variables (IVs), respectively. Our results showed that RA patients have a higher risk of getting CTS regardless of whether the ebi database (IVW, OR = 1.045, 95% CI: 1.016–1.075, P = 0.002) or the GEO database (IVW, OR = 1.001, 95% CI: 1.001–1.002, P = 0.001) is selected for CTS data. However, the MR analysis showed no causal link between CTS and the increased risk of RA (ebi: IVW, OR = 1.084, 95% CI: 0.918–1.279, P = 0.341; GEO: IVW, OR = 1.968, 95% CI: 0.011–360.791, P = 0.799). Conclusion: The analysis revealed that RA can increase the risk of CTS, but did not support the causal relationship that CTS can increase the risk of RA. [ABSTRACT FROM AUTHOR]

Rhododendron is a significant plant genus, with over 600 identified species in China. The subgenus Hymenanthes holds the largest number of Rhododendron germplasms and showcases strong environmental adaptability. However, there remains a lack of understanding regarding Rhododendron's evolution and environmental adaptations. Rhododendron bailiense Y.P.Ma, C.Q.Zhang & D.F.Chamb., an exceedingly rare species, thrives in the alkaline karst landforms of Guizhou, southwest China, different from the typical growing environment of other Rhododendron species. In this study, we present a chromosome‐level genome assembly of R. bailiense, revealing a genome size of 923.3 Mb, a contig N50 of 24.5 Mb, and a total of 47 567 predicted genes. An evolutionary analysis indicated that R. bailiense diverged from its ancestors prior to the other subgenus Hymenanthes rhododendrons, with the expanded and contracted genes being notably enriched in “stress response” and “growth,” respectively. Rhododendron bailiense is predominantly found on limestone soil in the mountains of Guizhou, with only two wild populations known. The genome of R. bailiense contained a high copy number of ankyrin repeat (ANK) and Ca2+‐ATPase (CAP) genes, primarily involved in Ca2+ transport, shedding light on how R. bailiense copes with karst high‐calcium stress. In contrast, the structures of the ANKs displayed unique characteristics, while the CAPs showed conservatism. The R. bailiense genome provides new insights into the adaptation and evolutionary history of Rhododendron plants in karst environments, potentially offering valuable information for adaptive breeding and ecological enhancement in such challenging settings. [ABSTRACT FROM AUTHOR]

Background: There have been some studies on the occurrence of ESR1 and 2 polymorphisms and AIS, but some data extraction is wrong, and there are no studies on the progress of AIS. Methods: Computer searches were conducted on PubMed, EMBASE, ScienceDirect and Scopus from the establishment of the database to April 2024. Cross-sectional and case-control studies on estrogen receptor ESR1, two single nucleotide polymorphisms, and the occurrence and development of AIS were collected, and statistical analysis was performed using the Revman 5.3 software. Results: In the comparison of the association between single nucleotide polymorphisms of estrogen receptors ESR1 and 2 and the occurrence and development of AIS, eight studies were included, including 2706 cases and 1736 controls.The results showed that the AA genotype [OR = 0.50,95%Cl(0.34,0.72),P = 0.0003] at the XbaI locus of ESR1,CC genotype [OR = 1.67,95%Cl(1.16,2.42), P = 0.006], C allele [OR = 1.28,95%Cl(1.03,1.59),P = 0.03], and T allele [OR = 0.78,95%] Cl(0.63,0.97),P = 0.03] at the PvuII locus of ESR1 and TT genotype [OR = 0.50,95%Cl(0.26,0.93),P = 0.03] at the AlwNI locus of ESR2 showed statistically significant differences between the progressive and stable AIS patients. Conclusion: Single nucleotide polymorphisms of ESR1 and ESR2 were not related to the occurrence of AIS; however, some of them were related to the progression of AIS. [ABSTRACT FROM AUTHOR]

Background : Diplomonads are anaerobic flagellates classified within Metamonada. They contain both host-associated commensals and parasites that reside in the intestinal tracts of animals, including humans (e.g., Giardia intestinalis), as well as free-living representatives that inhabit freshwater and marine anoxic sediments (e.g., Hexamita inflata). The evolutionary trajectories within this group are particularly unusual as the free-living taxa appear to be nested within a clade of host-associated species, suggesting a reversal from host-dependence to a secondarily free-living lifestyle. This is thought to be an exceedingly rare event as parasites often lose genes for metabolic pathways that are essential to a free-living life strategy, as they become increasingly reliant on their host for nutrients and metabolites. To revert to a free-living lifestyle would require the reconstruction of numerous metabolic pathways. All previous studies of diplomonad evolution suffered from either low taxon sampling, low gene sampling, or both, especially among free-living diplomonads, which has weakened the phylogenetic resolution and hindered evolutionary insights into this fascinating transition. Results: We sequenced transcriptomes from 1 host-associated and 13 free-living diplomonad isolates; expanding the genome scale data sampling for diplomonads by roughly threefold. Phylogenomic analyses clearly show that free-living diplomonads form several branches nested within endobiotic species. Moreover, the phylogenetic distribution of genes related to an endobiotic lifestyle suggest their acquisition at the root of diplomonads, while traces of these genes have been identified in free-living diplomonads as well. Based on these results, we propose an evolutionary scenario of ancestral and derived lifestyle transitions across diplomonads. Conclusions: Free-living taxa form several clades nested within endobiotic taxa in our phylogenomic analyses, implying multiple transitions between free-living and endobiotic lifestyles. The evolutionary history of numerous virulence factors corroborates the inference of an endobiotic ancestry of diplomonads, suggesting that there have been several reversals to a free-living lifestyle. Regaining host independence may have been facilitated by a subset of laterally transferred genes. We conclude that the extant diversity of diplomonads has evolved from a non-specialized endobiont, with some taxa becoming highly specialized parasites, others becoming free-living, and some becoming capable of both free-living and endobiotic lifestyles. Highlights: • Expanding the taxon sampling of phylogenomic analyses for diplomonads by sequencing transcriptomes of 13 free-living isolates and one endobiotic isolate. • Constructing a well-resolved evolutionary framework for exploring lifestyle adaptation in diplomonads using a phylogenomic approach. • Identifying genetic signatures of parasitic ancestry (variant-specific surface proteins, virulence factors) in free-living diplomonads. [ABSTRACT FROM AUTHOR]

The three‐dimensional architecture of the bacterial chromosome is intertwined with genome processes such as transcription and replication. Conspicuously so, that the structure of the chromosome permits accurate prediction of active genome processes. Although appreciation of this interplay has developed rapidly in the past two decades, our understanding of this subject is still in its infancy, with research primarily focusing on how the process of transcription regulates and is regulated by chromosome structure. Here, we summarize the latest developments in the field with a focus on the interplay between chromosome structure and transcription in Escherichia coli (E. coli) as mediated by H‐NS—a model nucleoid structuring protein. We describe how the organization of chromosomes at the global and local scales is dependent on transcription, and how transcription is regulated by chromosome structure. Finally, we take note of studies that highlight our limited knowledge of structure‐function relationships in the chromosome, and we point out research tracks that will improve our insight in the topic. [ABSTRACT FROM AUTHOR]

Fritillaria is a taxonomically complex genus of Liliaceae that contains many important ornamental and medicinal species. In this study, we sequenced the chloroplast genomes of ten Fritillaria species distributed in central Asia and compared them to previously sequenced Fritillaria cp genomes. Comparison of 36 Fritillaria species' cp genomes identified as useful potential molecular markers due to their high level of divergence three coding regions and 11 intergenic spacers. Effective single sequence repeats (SSRs) for population genetic studies of Fritillaria were also identified. Phylogenetic analysis showed that two recently described species, F. baisunensis and F. rugillosa belong to F. subg. Rhinopetalum, and that the belonging of F. ussuriensis and F. meleagroides in F. subg. Fritillaria should be revised. These two species and F. camschatsencese currently assigned to F. subg. Liliorhiza, should be members of the same taxonomic unit. Fritillaria subg. Liliorhiza, although a small group, is more complicated than it was previously thought, and apparently comprises species too distant to be in one subgenus. Fritillaria maximowischii, currently assigned to F. subg. Liliorhiza should be treated as a new subgenus. [ABSTRACT FROM AUTHOR]

More than 50 years have elapsed since the association of human leukocyte antigens (HLA) with type 1 diabetes (T1D) was first reported. Since then, methods for identification of HLA have progressed from cell based to DNA based, and the number of recognized HLA variants has grown from a few to tens of thousands. Current genotyping methodology allows for exact identification of all HLAencoding genes in an individual's genome, with statistical analysis methods evolving to digest the enormous amount of data that can be produced at an astonishing rate. The HLA region of the genome has been repeatedly shown to be the most important genetic risk factor for T1D, and the original reported associations have been replicated, refined, and expanded. Even with the remarkable progress through 50 years and over 5,000 reports, a comprehensive understanding of all effects of HLA on T1D remains elusive. This report represents a summary of the field as it evolved and as it stands now, enumerating many past and present challenges, and suggests possible paradigm shifts for moving forward with future studies in hopes of finally understanding all the ways in which HLA influences the pathophysiology of T1D. [ABSTRACT FROM AUTHOR]

In nature, diploids and tetraploids are two common types of polyploid evolution. Misgurnus anguillicaudatus (mud loach) is a remarkable fish species that exhibits both diploid and tetraploid forms. However, reconstructing the four haplotypes of its autotetraploid genome remains unresolved. Here, we generated the first haplotype-resolved, chromosome-level genome of autotetraploid M. anguillicaudatus with a size of 4.76 Gb, contig N50 of 6.78 Mb, and scaffold N50 of 44.11 Mb. We identified approximately 2.9 Gb (61.03% of genome) of repetitive sequences and predicted 91,485 protein-coding genes. Moreover, allelic gene expression levels indicated the absence of significant dominant haplotypes within the autotetraploid loach genome. This genome will provide a valuable biological model for unraveling the mechanisms of polyploid formation and evolution, adaptation to environmental changes, and benefit for aquaculture applications and biodiversity conservation. [ABSTRACT FROM AUTHOR]

The bay scallop, Argopecten irradians, is a species of major commercial, cultural, and ecological importance. It is endemic to the eastern coast of the United States, but has also been introduced to China, where it supports a significant aquaculture industry. Here, we provide an annotated chromosome-level reference genome assembly for the bay scallop, assembled using PacBio and Hi-C data. The total genome size is 845.9 Mb, distributed over 1,503 scaffolds with a scaffold N50 of 44.3 Mb. The majority (92.9%) of the assembled genome is contained within the 16 largest scaffolds, corresponding to the 16 chromosomes confirmed by Hi-C analysis. The assembly also includes the complete mitochondrial genome. Approximately 36.2% of the genome consists of repetitive elements. The BUSCO analysis showed a completeness of 96.2%. We identified 33,772 protein-coding genes. This genome assembly will be a valuable resource for future research on evolutionary dynamics, adaptive mechanisms, and will support genome-assisted breeding, contributing to the conservation and management of this iconic species in the face of environmental and pathogenic challenges. [ABSTRACT FROM AUTHOR]

Most eukaryotes have one nucleus and nuclear genome per cell. Ciliates have instead evolved distinct nuclei that coexist in each cell: a silent germline vs. transcriptionally active somatic nuclei. In the best-studied model species, both nuclei can divide asexually, but only germline nuclei undergo meiosis and karyogamy during sex. Thereafter, thousands of DNA segments, called internally eliminated sequences (IESs), are excised from copies of the germline genomes to produce the streamlined somatic genome. In Loxodes, however, somatic nuclei cannot divide but instead develop from germline copies even during asexual cell division, which would incur a huge overhead cost if genome editing was required. Here, we purified and sequenced both genomes in Loxodes magnus to see whether their nondividing somatic nuclei are associated with differences in genome architecture. Unlike in other ciliates studied to date, we did not find canonical germline-limited IESs, implying Loxodes does not extensively edit its genomes. Instead, both genomes appear large and equivalent, replete with retrotransposons and repetitive sequences, unlike the compact, gene-rich somatic genomes of other ciliates. Two other hallmarks of nuclear development in ciliates--domesticated DDE-family transposases and editing-associated small RNAs--were also not found. Thus, among the ciliates, Loxodes genomes most resemble those of conventional eukaryotes. Nonetheless, base modifications, histone marks, and nucleosome positioning of vegetative Loxodes nuclei are consistent with functional differentiation between actively transcribed somatic vs. inactive germline nuclei. Given their phylogenetic position, it is likely that editing was present in the ancestral ciliate but secondarily lost in the Loxodes lineage. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma spp. are wall-less bacteria with small genomes (usually 0.5–1.5 Mb). Many Mycoplasma (M.) species are known to colonize the respiratory tract of both humans and livestock animals, where they act as primary pathogens or opportunists. M. equirhinis was described for the first time in 1975 in horses but has been poorly studied since, despite regular reports of around 14% prevalence in equine respiratory disorders. We recently showed that M. equirhinis is not a primary pathogen but could play a role in co-infections of the respiratory tract. This study was a set up to propose the first genomic characterization to better our understanding of the M. equirhinis species. Results: Four circularized genomes, two of which were generated here, were compared in terms of synteny, gene content, and specific features associated with virulence or genome plasticity. An additional 20 scaffold-level genomes were used to analyse intra-species diversity through a pangenome phylogenetic approach. The M. equirhinis species showed consistent genomic homogeneity, pointing to potential clonality of isolates despite their varied geographical origins (UK, Japan and various places in France). Three different classes of mobile genetic elements have been detected: insertion sequences related to the IS1634 family, a putative prophage related to M. arthritidis and integrative conjugative elements related to M. arginini. The core genome harbours the typical putative virulence-associated genes of mycoplasmas mainly involved in cytoadherence and immune escape. Conclusion: M. equirhinis is a highly syntenic, homogeneous species with a limited repertoire of mobile genetic elements and putative virulence genes. [ABSTRACT FROM AUTHOR]

We assess the UK Biobank (UKB) Polygenic Risk Score (PRS) Release, a set of PRSs for 28 diseases and 25 quantitative traits that has been made available on the individuals in UKB, using a unified pipeline for PRS evaluation. We also release a benchmarking software tool to enable like-for-like performance evaluation for different PRSs for the same disease or trait. Extensive benchmarking shows the PRSs in the UKB Release to outperform a broad set of 76 published PRSs. For many of the diseases and traits we also validate the PRS algorithms in a separate cohort (100,000 Genomes Project). The availability of PRSs for 53 traits on the same set of individuals also allows a systematic assessment of their properties, and the increased power of these PRSs increases the evidence for their potential clinical benefit. [ABSTRACT FROM AUTHOR]