G3: Genes|Genomes|Genetics最新文献

The explosion of genomic and multiomics data has created a need for scalable, reproducible tools that integrate functional annotations into genome-wide association studies (GWAS). We introduce the multiomics data bridged Kernel Association test (MOKA) pipeline, a Snakemake-based workflow that automates SNP-set kernel-based association testing by incorporating multiomics data, including gene expression, transcription factor binding, evolutionary conservation scores, and neural network-derived features. This data-bridged architecture enhances variant prioritization and aggregation, improving statistical power in GWAS. MOKA supports population structure correction via spectral decomposition, parallel computation, and post-GWAS analyses, including visualization, Gene Ontology annotation, pathway enrichment, and validation. As a use case, we applied MOKA to a schizophrenia GWAS cohort, identified 89 Bonferroni-significant genes, with a 15.7% validation rate in the disease-specific DisGeNET database and enrichment in pathways relevant to neuropsychiatric disease. MOKA provides a robust, scalable, and extensible framework for functional multiomics integration in genetic studies. It is open-source and available at https://github.com/davidenoma/moka.

The anchor cell (AC) of the Caenorhabditis elegans hermaphrodite somatic gonad primordium is a signaling nexus that regulates uterine and vulval development. As the somatic gonad primordium is forming, four cells, two α and two β cells, are born with the potential to be the AC. This potential becomes restricted to the α cells, which undergo the LIN-12/Notch-mediated AC/VU decision to resolve which α cell will become the AC. The transcription factor HLH-2, the sole E/Daughterless protein ortholog in C. elegans, is critical for this process, and dynamic regulation of hlh-2 transcription contributes to the robust specification of a single AC. The hlh-2prox regulatory element mediates the dynamic pattern of hlh-2 transcription: the initial expression in the parents of the α and β cells, which is briefly sustained in the α and β cells after they are born; its subsequent restriction to the α cells during the AC/VU decision; and its continued expression in the AC. In this study, we identify the cis-acting sequences within hlh-2prox and transcription factors required for the initial expression of hlh-2 in the α and β cells and their parents, demonstrate that the Wnt/β-catenin Asymmetry Pathway (WβA) regulates restriction of hlh-2 transcription to the α cells, and show that the maintenance of hlh-2 transcription in α cells requires distinct elements and the chromatin factor LSY-12. This analysis extends our understanding of regulatory mechanisms that operate during a precise and robust Notch-mediated lateral specification paradigm.

With the advent of long-read DNA sequencing technologies, assembling eukaryotic genomes has become routine; however, properly phasing the maternal and paternal contributions, which is of great value for breeding programs, remains technically challenging. Here, we use the trio-binning approach to separate Oxford Nanopore reads derived from a Cannabis F1 wide cross, made between the Colombian landrace Punto Rojo and the Colorado CBD clone Cherry Pie #16. Reads were obtained from a single PromethION flow cell, generating assemblies with coverage of just 18 × per haplotype, but with good contiguity and gene completeness, demonstrating that it is a cost-effective approach for genome-wide and high-quality haplotype phasing. Evaluated through the lenses of disease resistance and secondary metabolite synthesis, both being traits of interest for the Cannabis industry, we report copy number and structural variation that, as has recently been shown for other major crops, may contribute to phenotypic variation along several relevant dimensions.

Gene-environment interactions (G×E) have been shown to explain a non-negligible proportion of variance for a plethora of complex traits in different species, including livestock, plants, and humans. While several studies have shown that including G×E can improve prediction accuracy in agricultural species, no increase in accuracy has been observed in human studies. In this work, we sought to investigate the scenarios in which accounting for G×E is expected to improve prediction accuracy. Model organisms are useful for studying G×E, since environments can be defined precisely, and genotypes can be replicated across environments, which are ideal conditions to minimize confounding in G×E analyses. Thus, we used data from an experiment in Drosophila melanogaster, where researchers measured lifespan in different environments for unrelated inbred lines (i.e. genotypes). We used three different cross-validation (CV) scenarios that mimic different relationships between reference and test populations, and fitted a few statistical models with and without including G×E. The results showed that G×E explained 8% of lifespan variance. Despite that, models accounting for G×E improved prediction accuracy only in CV scenarios where the same genotypes are observed in both the reference and test populations. While these scenarios are common in agriculture, where individuals of the same family or variety appear in both populations, they are not commonly encountered in human studies, where individuals are unrelated. Thus, our work shows in which prediction scenarios we can expect improvements by accounting for G×E, and may provide a potential reason (among others) for results of human studies.

Octopamine (OA), the insect analog of noradrenaline, plays important roles in diverse behavioral and physiological processes, from modulating fight-or-flight behavior to regulating postmating ovulation. In Drosophila, 6 OA receptors have been identified: Oamb, Octα2R, Octβ1R, Octβ2R, Octβ3R, and Oct-TyrR, and they have been linked to different behavioral and physiological processes. Here, we investigated the evolutionary characteristics of these receptors across Drosophila species. We found that OA receptors are generally found as single-copy genes. Notably, Octβ2R and Octβ3R exhibit positive selection within the melanogaster species group, though in different structural regions from one another. The positively selected sites in Octβ2R are exclusively located in regions important for ligand binding, whereas those in Octβ3R are predominantly found in regions crucial for signal transduction. Interestingly, Octβ2R remains highly conserved outside the melanogaster species group, so the detection of positive selection in its ligand binding-related domains within this clade raises the possibility that it has evolved an additional, melanogaster-specific ligand interaction, among other potential reasons. These findings highlight the evolutionary flexibility of aminergic signaling and suggest lineage-specific adaptations of OA receptor function in Drosophila, likely shaped by lineage-specific selective pressures.

Hybridization is a major force driving diversification, migration, and adaptation in Quercus species. While population genetics and phylogenetics have traditionally been used for studying these processes, advances in sequencing technology now enable us to incorporate comparative and pan-genomic approaches as well. Here we present a highly contiguous, chromosome-scale and haplotype-resolved genome assembly for the southern live oak, Quercus virginiana, the first reference genome for section Virentes, as part of the American Campus Tree Genomes (ACTG) program. Originating from a clone of Auburn University's historic "Toomer's Oak," this assembly contributes to the pool of genomic resources for investigating recombination, haplotype variation, and structural genomic changes influencing hybridization potential in this clade and across Quercus. It also provides insights into the architecture of the putative centromeric regions within the genus. Alongside other oak references, the Q. virginiana genome will support research into the evolution and adaptation of the Quercus genus.

Istocheta aldrichi Mesnil 1953 (Diptera: Tachinidae), is native to Japan, and has recently become an important biological control agent of the Japanese beetle, Popillia japonica (Coleoptera: Scarabaeidae), a pest with >300 host plants, including roses, linden trees, and numerous agricultural crops. During the past decade, I. aldrichi's range has greatly expanded across North America, particularly in Quebec and Ontario, Canada, and in the Midwest U.S. In Minnesota, parasitism of Japanese beetles by I. aldrichi was documented in commercial apple orchards in 2021, and has since spread to multiple locations, highlighting its importance as a natural enemy. To facilitate research on I. aldrichi and other tachinid flies we present a haploid reference genome generated from a single unsexed individual. The final genome assembly is 875.3 Mbp contained in 1,041 scaffolds, with an N50 of 4.77 Mbp, and 99.5% complete Diptera BUSCOs present. We also present a complete mitogenome and use comparative genomics across 19 tachinid species to identify unique features of I. aldrichi. Specifically, we find that tachinids as a whole have undergone rapid copy number changes in 935 gene families, largely related to metabolism and morphogenesis. While many tachinid lineages have experienced contractions in gene families, I. aldrichi is characterized by a relatively high number of gene family expansions, many of which are predicted to function in metal ion transport. The I. aldrichi reference genome will further research opportunities on these parasitic flies, including their potential for biocontrol of P. japonica.

A novel method for mapping the interphase genome architecture in Drosophila polytene chromosomes is proposed. The method is based on physical mapping of the boundaries between interbands, gray bands, and black bands. Mapping relies on three criteria: the 4HMM bioinformatic model that considers the associations between each of the four chromatin states and polytene chromosome structures and the findings of ChIP-seq analysis in salivary glands for two critical markers: the CHRIZ/CHRO protein localized in housekeeping gene promoters and H3K36me3 histone modification, a marker of transcriptional elongation. For mapping the 1AF region of the X chromosome, FISH probes were selected from AQUAMARINE chromatin (interbands) at the boundary with black bands, which provided precise coordinates of the edges of black bands (localization of the developmental genes). The localization of promoters and housekeeping gene bodies was then identified by ChIP-seq analysis for CHIRIZ and H3K36me3 in salivary glands (the interbands and gray bands, respectively). These maps will allow one to better understand the architecture of an actively functioning genome.

Genome sequence contamination has a variety of causes and can originate from within or between species. Previous research focused on contamination between distantly related species or on prokaryotes. Here we test for intra-species contamination by mapping short read genome data to a reference and visualizing the frequency of reads with single nucleotide di_erences from the reference. Out of 1,298 publicly available genome sequences investigated for Saccharomyces cerevisiae, a small number (8 genomes) show at least 5% contamination. Contamination rates di_ered however among sequencing centers: one unusually large study had a low contamination rate (below 0.2%) but the contamination rate was higher for other studies (2% or 15% of genomes). Using genome data contaminated in silico to known degrees, we showed that contamination is recognizable in plots with unexpected secondary allele (B-allele) frequencies of at least 5% and measured contamination e_ects on admixture and phylogenetic analysis in two fungal species. With a standard base calling pipeline, we found that contaminated genomes super_cially appeared to produce good quality genome data. Yet as little as 5-10% genome contamination was enough to change phylogenetic tree topologies and make contaminated strains appear as hybrids between lineages (genetically admixed). We recommend the use of B-allele frequency plots to screen genome resequencing data for intra-species contamination.