G3: Genes|Genomes|Genetics最新文献

Plasmopara viticola, the causal agent of grapevine downy mildew, is a biotrophic oomycete engaged in a tight coevolutionary relationship with its host. Rapid adaptation of the pathogen is favored by annual sexual reproduction that generates genotypic diversity. With the aim of studying the recombination landscape across the P. viticola genome, we generated 2 half-sibling F1 progenies (N = 189 and 162). Using targeted SNP sequencing, between 1,405 and 1,894 markers were included in parental linkage maps, and a consensus map was obtained by integrating 4,509 markers. The reference genome could be assembled into 17 pseudochromosomes, anchoring 88% of its physical length. We observed a strong collinearity between parental genomes and extensive synteny with the downy mildew Peronospora effusa. In the consensus map, the median recombination rate was 13.8 cM/Mb. The local recombination rate was highly variable along chromosomes, and recombination was suppressed in putative centromeric regions. Recombination rate was found negatively correlated with repeats' coverage and positively correlated with gene coverage. However, genes encoding secreted proteins and putative effectors were underrepresented in highly recombining regions. In both progenies, about 5% of the individuals presented karyotypic anomalies. Aneuploidies and triploidies almost exclusively originated from the male-transmitted chromosomes. Triploids resulted from fertilization by diploid gametes, but also from dispermy. Obligatory sexual reproduction each year may explain the lower level of karyotypic variation in P. viticola compared to other oomycetes. The linkage maps will be useful to guide future de novo chromosome-scale assemblies of P. viticola genomes and to perform forward genetics.

Features of the natural life cycle of the budding yeast Saccharomyces cerevisiae were crucial to its domestication as a laboratory experimental model, especially the ability to maintain stable haploid clones and cross them at will to combine alleles via meiosis. Stable haploidy results from mutations in HO, which encodes an endonuclease required for haploid-specific mating-type switching. Previous studies found an unexpected diversity of HO alleles among natural isolates within a small geographic area. We developed a hands-on field and laboratory activity for middle-school students in Denver, CO, USA, to isolate wild yeast from oak bark, identify species via DNA sequencing, and sequence HO from S. cerevisiae isolates. We find limited HO diversity in North American oak isolates, pointing to efficient, continuous dispersal across the continent. In contrast, we isolated the "dairy yeast," Kluyveromyces lactis, from a tree <10 m away and found that it represents a new population distinct from an oak population in an adjacent state. The outreach activity partnered middle-school, high-school, and university students in making scientific discoveries and can be adapted to other locations and natural yeast habitats. Indeed, a pilot sampling activity in southeast Texas yielded S. cerevisiae oak isolates with a new allele of HO and, from a nearby prickly pear cactus, a heat-tolerant isolate of Saccharomyces paradoxus.

Local adaptation is widely seen when species adapt to spatially heterogeneous environments. Although many theoretical studies have investigated the dynamics of local adaptation using 2-population models, there remains a need to extend the theoretical framework to continuous space settings, reflecting the real habitats of species. In this study, we use a multidimensional continuous space model and mathematically analyze the establishment process of local adaptation, with a specific emphasis on the relative roles of mutation and migration. First, the role of new mutations is evaluated by deriving the establishment probability of a locally adapted mutation using a branching process and a diffusion approximation. Next, the contribution of immigrants from a neighboring region with similar environmental conditions is considered. Theoretical predictions of the local adaptation rate agreed with the results of Wright-Fisher simulations in both mutation-driven and migration-driven cases. Evolutionary dynamics depend on several factors, including the strength of migration and selection, population density, habitat size, and spatial dimensions. These results offer a theoretical framework for assessing whether mutation or migration predominantly drives convergent local adaptation in spatially continuous environments in the presence of patchy regions with similar environmental conditions.

Lotmaria passim is a ubiquitous trypanosomatid parasite of honey bees nestled within the medically important subfamily Leishmaniinae. Although this parasite is associated with honey bee colony losses, the original draft genome-which was completed before its differentiation from the closely related Crithidia mellificae-has remained the reference for this species despite lacking improvements from newer methodologies. Here, we report the updated sequencing, assembly, and annotation of the BRL-type (Bee Research Laboratory) strain (ATCC PRA-422) of Lotmaria passim. The nuclear genome assembly has been resolved into 31 complete chromosomes and is paired with an assembled kinetoplast genome consisting of a maxicircle and 30 minicircle sequences. The assembly spans 33.7 Mb and contains very little repetitive content, from which our annotation of both the nuclear assembly and kinetoplast predicted 10,288 protein-coding genes. Analyses of the assembly revealed evidence of a recent chromosomal duplication event within chromosomes 5 and 6 and provided evidence for a high level of aneuploidy in this species, mirroring the genomic flexibility employed by other trypanosomatids as a means of adaptation to different environments. This high-quality reference can therefore provide insights into adaptations of trypanosomatids to the thermally regulated, acidic, and phytochemically rich honey bee hindgut niche, which offers parallels to the challenges faced by other Leishmaniinae during the challenges they undergo within insect vectors, during infection of mammals, and exposure to antiparasitic drugs throughout their multi-host life cycles. This reference will also facilitate investigations of strain-specific genomic polymorphisms, their role in pathogenicity, and the development of treatments for pollinator infection.

GenoTools, a Python package, streamlines population genetics research by integrating ancestry estimation, quality control, and genome-wide association studies capabilities into efficient pipelines. By tracking samples, variants, and quality-specific measures throughout fully customizable pipelines, users can easily manage genetics data for large and small studies. GenoTools' "Ancestry" module renders highly accurate predictions, allowing for high-quality ancestry-specific studies, and enables custom ancestry model training and serialization specified to the user's genotyping or sequencing platform. As the genotype processing engine that powers several large initiatives, including the NIH's Center for Alzheimer's and Related Dementias and the Global Parkinson's Genetics Program, GenoTools was used to process and analyze the UK Biobank and major Alzheimer's disease and Parkinson's disease datasets with over 400,000 genotypes from arrays and 5,000 whole genome sequencing samples and has led to novel discoveries in diverse populations. It has provided replicable ancestry predictions, implemented rigorous quality control, and conducted genetic ancestry-specific genome-wide association studies to identify systematic errors or biases through a single command. GenoTools is a customizable tool that enables users to efficiently analyze and scale genotyping and sequencing (whole genome sequencing and exome) data with reproducible and scalable ancestry, quality control, and genome-wide association studies pipelines.

As human complex diseases are influenced by the interaction between genetics and the environment, identifying gene-environment interactions (G×E) is crucial for understanding disease mechanisms and predicting risk. Developing robust quantitative tools for G×E analysis can enhance the study of complex diseases. However, many existing methods that explore G×E focus on the interplay between an environmental factor and genetic variants, exclusively for common or rare variants. In this study, we developed MAGEIT_RAN and MAGEIT_FIX to identify interactions between an environmental factor and a set of genetic markers, including both rare and common variants, based on the MinQue for Summary statistics. The genetic main effects in MAGEIT_RAN and MAGEIT_FIX are modeled as random and fixed effects, respectively. Simulation studies showed that both tests had type I error under control, with MAGEIT_RAN being the most powerful test. Applying MAGEIT to a genome-wide analysis of gene-alcohol interactions on hypertension and seated systolic blood pressure in the Multiethnic Study of Atherosclerosis revealed genes like EIF2AK2, CCNDBP1, and EPB42 influencing blood pressure through alcohol interaction. Pathway analysis identified 1 apoptosis and survival pathway involving PKR and 2 signal transduction pathways associated with hypertension and alcohol intake, demonstrating MAGEIT_RAN's ability to detect biologically relevant gene-environment interactions.

This study aimed to broaden applicability of KASP for Oryza sativa across diverse genotypes through incorporation of ambiguous (degenerate) bases into their primer designs and to validate 4,000 of them for genotyping applications. A bioinformatics pipeline was used to compare 129 rice genomes from 89 countries with the indica reference genome R498 and generate ∼1.6 million KASP designs for the more common variants between R498 and the other genomes. Of the designs, 98,238 were for predicted functional markers. Up to 5 KASP each for 1,024 breeder-selected loci were assayed in a panel of 178 diverse rice varieties, generating 3,366 validated KASP. The 84% success rate was within the normal range for KASP demonstrating that the ambiguous bases do not compromise efficacy. The 3,366-trait-specific marker panel was applied for population structure analysis in the diversity panel and resolved them into 4 expected groups. Target variations in 13 genomes used for designs were compared with the corresponding KASP genotypes in different accessions of the same 13 varieties in the diversity panel. There was agreement for 79% or more markers in 12 varieties; 10 having agreement >88%. One variety, a selection from a landrace, had only 46.5% marker agreement. Breeders can search for the validated KASP and more than a million so-far untested designs in three reference genomes (including Niponbare MSU7) with a search tool, that includes designs in proximity to previously published microsatellite markers, and retrieve target variations for 129 rice genomes plus their genomic locations with ±25 bp flanking sequences.

Glial cells are known to influence neuronal functions through glia-neuron communication. The present study aims to elucidate the mechanism behind peroxisome-mediated glia-neuron communication using Drosophila neuromuscular junction (NMJ) as a model system. We observe a high abundance of peroxisomes in the abdominal NMJ of adult Drosophila. Interestingly, glia-specific knockdown of peroxisome import receptor protein, Pex5, significantly increases axonal area and volume and leads to axon swelling. The enlarged axonal structure is likely deleterious, as the flies with glia-specific knockdown of Pex5 exhibit age-dependent locomotion defects. In addition, impaired peroxisomal ether lipid biosynthesis in glial cells also induces axon swelling. Consistent with our previous work, defective peroxisomal import function upregulates pro-inflammatory cytokine upd3 in glial cells, while glia-specific overexpression of upd3 induces axonal swelling. Furthermore, motor neuron-specific activation of the JAK-STAT pathway through hop overexpression results in axon swelling. Our findings demonstrated that impairment of glial peroxisomes alters axonal morphology, neuroinflammation, and motor neuron function.

The Jonah crab, Cancer borealis, is integral to marine ecosystems and supports a rapidly growing commercial fishery in the northwest Atlantic Ocean. This species also has a long history as a model for neuroscience that has expanded our understanding of central pattern generators, neuromodulation, synaptic plasticity, and the connectivity of neural circuits. Here, we present a highly contiguous reference genome for the Jonah crab that will provide an essential resource to advance fisheries, conservation, and biomedical research. Using a combination of PacBio long-read sequencing and Omni-C scaffolding, we generated a final genome assembly spanning 691 Mb covering 51 chromosome-length scaffolds and 106 additional contigs. Benchmarking Universal Single-Copy Ortholog (BUSCO) analysis indicated a high-quality assembly with a completeness score of 90.8%. Repeat annotation identified 1,649 repeat families making up 48.27% of the Jonah crab genome. Gene model predictions annotated 24,830 protein coding genes with a 92.3% BUSCO score. Gene family evolution analysis revealed the expansion of gene families associated with nervous system function, and targeted analysis revealed an extensive repertoire of neural genes. The Jonah crab genome will not only provide a resource for neuroscience research but will also serve as a foundation to investigate adaptation to stress and population structure to support sustainable fisheries management during this time of rapidly changing environmental conditions in the northwest Atlantic Ocean.

Non-muscle myosin (NMII) motor proteins have diverse developmental functions due to their roles in cell shape changes, cell migration, and cell adhesion. Zebrafish are an ideal vertebrate model system to study the NMII encoding myh genes and proteins due to high sequence homology, established gene editing tools, and rapid ex utero development. In humans, mutations in the NMII encoding MYH genes can lead to abnormal developmental processes and disease. This study utilized zebrafish myh9a, myh9b, and myh10 null mutants to examine potential genetic interactions and roles for each gene in development. It was determined that the myh9b gene is the most critical NMII encoding gene, as myh9b mutants develop pericardial edema and have a partially penetrant lethal phenotype, which was not observed in the other myh mutants. This study also established that genetic interactions occur between the zebrafish myh9a, myh9b, and myh10 genes where myh9b is required for the expression of both myh9a and myh10, and myh10 is required for the expression of myh9b. Additionally, protein analyses suggested that enhanced NMII protein stability in some mutant backgrounds may play a role in compensation. Finally, double mutant studies revealed different and more severe phenotypes at earlier time points than single mutants, suggesting roles for tissue specific genetic redundancy, and in some genotypes, haploinsufficiency. These mutants are the first in vivo models allowing for the study of complete loss of the NMIIA and NMIIB proteins, establishing them as valuable tools to elucidate the role of NMII encoding myh genes in development and disease.