Biology subjects

Davenport, R.

Publications and source records attributed to Davenport, R..

6 recordsLinked to original sources

bioRxiv2025

The genome of the vining fern Lygodium microphyllum highlights genomic and functional differences between life phases of an invasive plant

Functional and genomic studies on the differences between gametophyte and sporophyte life phases remain scarce, yet unraveling these dynamics is crucial to understanding the biology of plants and the success of each phase under different environments. Here, we provide a novel reference genome for the highly invasive fern Lygodium microphyllum and compare the transcriptomic and epigenomic landscapes of the gametophyte and sporophyte life phases. We found differential regulation of developmental genes (homeobox and MADS-box clades) and usage of alternative isoforms that may play a role in the genomic determination of the haploid and diploid life stages. We further generated the first base pair-resolution methylome of a fern gametophyte, and determined that methylation patterns are remarkably similar between vegetative tissues despite their morphological and functional differences. By examining the physiological and transcriptomic responses of gametophytes and sporophytes to freezing stress, the most likely abiotic factor preventing further expansion of this invasive species, we show that life phases and tissues use alternative molecular pathways to respond to this stressor, underscoring the need to incorporate both life phases when developing effective mitigation strategies. These new genomic resources fill a gap in our understanding of fundamental plant biology and inform invasive species research. SIGNIFICANCEAll land plants undergo an alternation of generations between haploid gametophyte and diploid sporophyte life phases. How these disparate life phases are generated from a single genome, and the functional implications of these differences for plant success, is largely unknown. Moreover, understanding life-phase-specific differences in rapidly evolving populations, such as invasive species, is critical to developing effective management strategies. We assembled a chromosome-level genome and generated epigenomic and transcriptomic resources from gametophyte and sporophyte phases of the invasive fern Lygodium microphyllum, which is estimated to cost the U.S. more than $2 million annually. We highlight transcriptomic, epigenomic, and physiological variation between life phases and find support for the crucial role of the often overlooked gametophyte in the invasion process.

plant biology↗

bioRxiv2024

The probability and duration of immigration in microbial communities

Immigration is a fundamental feature of microbial communities. We propose a method to determine the probability (Pi) that a number of immigrants (i) can attain an abundance N using the ratio of the probabilities of death q and division or "birth" p and the gamblers ruin equation: Pi= (1-(q/p)i/(1-(q/p)N). We estimate the probability of successful bioaugmentation or transplantation, the fate of a mutation infection and extinction. For example, an inoculum of 108 bacteria with a q/p of 1.00000001 has a 10-43 chance of attaining an abundance of 1010. The immigration parameter used in neutral models, m is 1/(1-q/p). We calculated the long-term average value of m and q/p in a wastewater treatment plant. The value of m varies by >5 orders of magnitude, with a curious bimodal distribution. However, all the values of q/p are very close to, but greater than, 1. We expect the long-term average value of q/p to be [~]1 in all stable microbial communities. In the absence of migration, bacterial populations with a q/p [≥]1 will go extinct with probability 1. The link between q/p and infectious dose is known and we demonstrate that, in principle, the gamblers ruin equation can estimate the infectious dose in naturally occurring infections, using Vibrio cholerae "carriers" to illustrate the point. We use the ratio q/p to estimate the time (measured in events or solar time) for a given change in abundance to happen. When q/p=1, extinction in even a small microbial population will take thousands of years.

microbiology↗

bioRxiv2020

Evolutionary Conservation and Essential Function of Human and Maize RNA Binding Motif Protein 48 (RBM48) in U12-Type Intron Splicing

U12-type or minor introns are found in most multicellular eukaryotes and constitute [~]0.5% of all introns in species with a minor spliceosome. Although the biological significance for evolutionary conservation of U12-type introns is debated, mutations disrupting U12 splicing cause developmental defects in both plants and animals. In human hematopoietic stem cells, U12 splicing defects disrupt proper differentiation of myeloid lineages and are associated with myelodysplastic syndrome (MDS), predisposing individuals to acute myeloid leukemia. Mutants in the maize ortholog of RNA Binding Motif Protein48 (RBM48) have aberrant U12-type intron splicing. Human RBM48 was recently purified biochemically as part of the minor spliceosome and shown to recognize the 5 end of the U6atac snRNA. In this report, we use CRISPR/Cas9-mediated ablation of RBM48 in human K-562 cells to show the genetic function of RBM48. RNA-seq analysis comparing wild-type and mutant K-562 genotypes found that 48% of minor intron containing genes (MIGs) have significant U12-type intron retention in RBM48 mutants. Comparing these results to maize rbm48 mutants defined a subset of MIGs disrupted in both species. Mutations in the majority of these orthologous MIGs have been reported to cause developmental defects in both plants and animals. Our results provide genetic evidence that the primary defect of human RBM48 mutants is aberrant U12-type intron splicing, while a comparison of human and maize RNA-seq data identifies candidate genes likely to mediate mutant phenotypes of U12-type splicing defects.

evolutionary biology↗

bioRxiv2019

Single- nuclei RNA sequencing from human brain to study for Mendelian and sporadic AD

Alzheimer Disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures. Using bulk RNA-seq from parietal lobes and deconvolution methods, we previously reported that brains exhibiting different AD genetic architecture exhibit different cellular proportions. Here, we sought to directly investigate AD brain changes in cell proportion and gene expression using single cell resolution. To do so, we generated unsorted single-nuclei RNA-sequencing data from brain tissue. We leveraged tissue donated from a carrier of a Mendelian genetic mutation and two family members who suffer from AD, but do not have the same mutation. We evaluated alternative alignment approaches to maximize the titer of reads, genes and cells with high quality. In addition, we employed distinct clustering strategies to determine the best approach to identify cell clusters that reveal neuronal and glial cell types and avoid artifacts such as sample and batch effects. We propose an approach to cluster cells that reduces biases and enable further analyses. We identified distinct types of neurons, both excitatory and inhibitory, and glial cells, including astrocytes, oligodendrocytes, and microglia among others. In particular, we identified a reduced proportion of excitatory neurons in the Mendelian mutation carrier, but a similar distribution of inhibitory neurons. Furthermore, we investigated whether single-nuclei RNA-seq from human brains recapitulate the expression profile of Disease Associated Microglia (DAM) discovered in mouse models. We also determined that when analyzing human single-nuclei data it is critical to control for biases introduced by donor specific expression profiles. In conclusion, we propose a collection of best practices to generate a highly-detailed molecular cell atlas of highly informative frozen tissue stored in brain banks. Importantly, we have developed a new web application to make this unique single-nuclei molecular atlas publicly available.

genomics↗

bioRxiv2019

The TMEM106B rs1990621 protective variant is also associated with increased neuronal proportion

BackgroundIn previous studies, we observed decreased neuronal and increased astrocyte proportions in AD cases in parietal brain cortex by using a deconvolution method for bulk RNA-seq. These findings suggested that genetic risk factors associated with AD etiology have a specific effect in the cellular composition of AD brains. The goal of this study is to investigate if there are genetic determinants for brain cell compositions.\n\nMethodsUsing cell type composition inferred from transcriptome as a disease status proxy, we performed cell type association analysis to identify novel loci related to cellular population changes in disease cohort. We imputed and merged genotyping data from seven studies in total of 1,669 samples and derived major CNS cell type proportions from cortical RNAseq data. We also inferred RNA transcript integrity number (TIN) to account for RNA quality variances. The model we performed in the analysis was: normalized neuronal proportion [~] SNP + Age + Gender + PC1 + PC2 + median TIN.\n\nResultsA variant rs1990621 located in the TMEM106B gene region was significantly associated with neuronal proportion (p=6.40x10-07) and replicated in an independent dataset. The association became more significant as we combined both discovery and replication datasets in multi-tissue meta-analysis (p=9.42x10-09) and joint analysis (p=7.66x10-10). This variant is in high LD with rs1990622 (r2 = 0.98) which was previously identified as a protective variant in FTD cohorts. Further analyses indicated that this variant is associated with increased neuronal proportion in participants with neurodegenerative disorders, not only in AD cohort but also in cognitive normal elderly cohort. However, this effect was not observed in a younger schizophrenia cohort with a mean age of death < 65. The second most significant loci for neuron proportion was APOE, which suggested that using neuronal proportion as an informative endophenotype could help identify loci associated with neurodegeneration.\n\nConclusionThis result suggested a common pathway involving TMEM106B shared by aging groups in the present or absence of neurodegenerative pathology may contribute to cognitive preservation and neuronal protection.

neuroscience↗

bioRxiv2018

RNA Binding Motif Protein 48 is required for U12 splicing and maize endosperm differentiation

The last eukaryotic common ancestor had two classes of introns that are still found in most eukaryotic lineages. Common U2-type and rare U12-type introns are spliced by the major and minor spliceosomes, respectively. Relatively few splicing factors have been shown to be specific to the minor spliceosome. We found that the maize RNA Binding Motif Protein48 (RBM48) is a U12 splicing factor that functions to promote cell differentiation and repress cell proliferation. RBM48 is coselected with the U12 splicing factor, ZRSR2/RGH3. Protein-protein interactions between RBM48, RGH3, and U2 Auxiliary Factor (U2AF) subunits suggest major and minor spliceosome factors may form complexes during intron recognition. Human RBM48 interacts with ARMC7. Maize RBM48 and ARMC7 have a conserved protein-protein interaction. These data predict that RBM48 is likely to function in U12 splicing throughout eukaryotes and that U12 splicing promotes endosperm cell differentiation in maize.

plant biology↗