Biology subjects

Morris, G. P.

Publications and source records attributed to Morris, G. P..

At least 19 recordsLinked to original sources

bioRxiv2026

Pangenomics and machine learning reveal genetic variation to optimize carotenoids in sorghum grain

Enhancing grain carotenoid concentration to increase yellowness and provitamin A content in sorghum (Sorghum bicolor [L.] Moench) is a major breeding objective across sub-Saharan Africa. Carotenoid breeding is constrained by costly post-harvest phenotyping and can be accelerated through genetic markers that capture functional variation in key carotenoid biosynthesis genes. Zeaxanthin epoxidase (ZEP) is a major gene controlling sorghum grain carotenoid accumulation, and SNP-based KASP markers facilitate selection of high-carotenoid grain, although quantitative variation remains among lines carrying the favorable allele. We hypothesized that additional functional variation within ZEP and other carotenoid biosynthesis pathway genes contributes to this variation and can be revealed by a pangenome-informed analysis. Using a 33-member pangenome reference, we characterized sequence and structural variation at ZEP and other key carotenoid biosynthesis genes and applied pangenome-derived genotyping to study marker diversity associated with carotenoid accumulation. Evaluation of ZEP in the pangenome reference revealed previously uncharacterized structural variation that is absent from the BTx623 primary reference genome. A pangenome-based association analysis identified genetic markers associated with the accumulation of carotenoids which were specific to particular pangenome reference members, including in RTx430 and SRN39, both yellow endosperm lines. Machine learning identified markers in ZEP, {beta}-OH, ZDS, and Z-ISO as the most predictive for all carotenoid traits, suggesting a multi-locus genetic architecture underlies the accumulation of carotenoids in sorghum grain. By integrating sorghum pangenomic resources with machine learning, this study establishes a framework for pangenome-accelerated trait discovery and identifies new genetic targets for carotenoid biofortification in sorghum.

genomics↗

bioRxiv2026

Phenotyping replication is a major determinant of genomic predictive ability in sweet sorghum (Sorghum bicolor Moench)

Genomic selection can increase the rate of genetic gain in crop breeding programs, but its effectiveness depends on the reliability of phenotypic data, the size and composition of the training population (TP), and the statistical model used to estimate genomic breeding values. These design choices are especially important in resource-limited breeding programs, where additional replication, larger TPs, and more extensive genotyping compete for the same resources. Using empirical data from a sweet sorghum [Sorghum bicolor (L.) Moench] breeding population, developed by CHIBAS, we evaluated the effects of phenotyping replication, TP size, training-validation genomic relatedness, and genomic prediction (GP) model on predictive ability (PA). Grain yield, plant height, stem weight, and total soluble solids were evaluated across three field environments. Few studies in sorghum have examined these factors together with comparable empirical rigor. Increasing replication improved genomic heritability and PA for all traits and environments, with the largest gains observed for grain yield. Larger TPs and increased training-validation genomic relatedness also improved PA, but their effects were most significant when phenotype estimates were based on multiple replicates. Different GP models had comparable PA across all evaluated traits, with a few exceptions. These findings provide practical guidance for optimizing genomic selection in resource-limited sorghum breeding programs. ARTICLE SUMMARYGenomic selection can accelerate breeding only when the phenotypes used to train predictive models are reliable. Using a sweet sorghum breeding population evaluated in three Haitian field environments, we quantified how replication number, training population size, training-validation genomic relatedness, and prediction model affected genomic predictive ability for grain yield, plant height, stem weight, and total soluble solids. Replication increased genomic heritability and predictive ability for all traits, with the strongest effects for grain yield. Larger and more connected training populations improved prediction, particularly when evaluated with greater replication. These results provide practical guidance for resource-limited breeding programs. Core ideasO_LIIn this empirical sweet sorghum breeding population, phenotyping replication was the dominant factor explaining variation in genomic predictive ability across traits and environments. C_LIO_LIThe benefit of larger training populations and greater training-validation genomic relatedness increased when phenotype estimates were based on more replicates. C_LIO_LIGrain yield, the most environmentally sensitive trait evaluated, showed the largest response to improved replication and training-population design. C_LIO_LIBayesian models, rrBLUP, and GBLUP showed similar predictive abilities across traits and environments, suggesting that phenotyping and experimental design may be more important than model complexity. C_LI

genomics↗

bioRxiv2026

Functional genomic map of local adaptation in sorghum to guide allele mining

Genomic data from genebanks could be exploited to find alleles adapted to target environments for resilience breeding, but it can be difficult to prioritize among the thousands of accessions and millions of genomic variants. There are competing hypotheses for the molecular basis and architecture of local adaptations: e.g. whether cis-regulatory versus amino acid changing variants are more important; or whether small-effect, low pleiotropy versus large-effect, high pleiotropy variants are more important. Here, we compare a range of variant types and genomic contexts thought to influence effect size, pleiotropy, and selection for their role in local adaptation in 443 whole genome resequenced African sorghum landraces. We used genotype-environment associations (GEAs) as evidence of local adaptation. We found that GEA were particularly enriched in the vicinity of genes and depleted elsewhere. However, enrichment was strongest in likely cis-regulatory contexts: accessible chromatin, unmethylated regions, and in transposable elements close to genes. Near genes, there were clear peaks in GEAs at the transcription start site, where mutations are demonstrated to have the largest expression effects. Additionally, GEAs in accessible chromatin and unmethylated regions were better predictors of genetic variation in response to experimental drought than comparable loci. Having tested hypotheses about the variants underlying local adaptation, we can now use this knowledge of the importance of cis-regulatory variation in the search for new environmentally-adaptive alleles for plant improvement.

evolutionary biology↗

bioRxiv2026

Field and lab phenomics facilitate detection of genetic variation for iron deficiency chlorosis tolerance in sorghum

Bioavailability of iron, an essential micronutrient to plants, is low in alkaline or calcareous soils, which are prevalent across semi-arid production regions. Breeding efforts to increase tolerance to iron deficiency chlorosis (IDC) in sorghum, a major crop of semi-arid regions, are confounded by spatial variation of stress severity in field trials. Here we developed and validated two high-throughput phenotyping approaches to address this challenge, with multi-spectral aerial imaging in the field and a controlled-environment assay to isolate the effects of iron bioavailability. In the field, severity and uniformity of stress are highly predictive of genetic signals for IDC tolerance (R2 > 0.6 for soil pH metrics and H2). Plot-level data filtering for stress conditions based on control genotypes successfully addresses field spatial variation (unfiltered H2 = 0.18 vs. filtered H2 = 0.4). The controlled-environment assay proxies field stress using iron sources with differential bioavailability, evidenced by high heritability ( H2 = 0.98) and phenotypic differential for hybrid control genotypes that matches field performance. Finally, we show that assay phenotypes are suitable for genome-wide association studies in global germplasm. Together, these field and lab phenomic approaches can be deployed to understand genetics of IDC tolerance and develop crops resilient to alkaline soils. HIGHLIGHTStress severity and uniformity greatly impact detection of genetic signals underlying iron deficiency chlorosis tolerance in sorghum. A controlled-environment assay reduces spatial heterogeneity and improves assessment of tolerance genetics.

genetics↗

bioRxiv2026

A stable genomic variant for photoperiodic flowering plasticity to enhance grain mold escape and yield stability in sorghum

Grain mold severely constrains sorghum [Sorghum bicolor (L.) Moench] productivity and grain quality in subhumid environments. Photoperiod-sensitive flowering plays a key role in mold avoidance and yield stability along north-south rainfall gradients. In response to the high susceptibility of elite cultivars in subhumid zones of Senegal, we developed and characterized a recombinant inbred line (RIL) population derived from Nganda (grain mold-susceptible) and Grinkan (photoperiod-sensitive) varieties. The population was evaluated across three distinct agro-ecological zones over two years. Environmental indices derived from genotype-environmental interactions, together with defined growth windows, strongly influenced flag leaf appearance (FLA), a photoperiodic flowering trait. Plasticity parameters (intercept and slope) for environmental indices, FLA, grain mold severity, and yield enabled identification of loci contributing to flowering response, mold resistance, and yield stability. The maturity gene Ma1 and two QTLs for FLA, qFLA6.2 and qFLA6.3, were identified, stable across environments, and colocalized with grain mold and yield QTLs. The wild-type Ma1 allele from Grinkan delayed FLA and reduced grain mold damage but was not associated with increased yield. The Ma1 effect was confirmed using the developed breeder-friendly KASP marker, Sbv3.1_06_40312464K, in 174 F3 three-way cross families. Photoperiod-sensitive lines with intermediate-to-late FLA alleles showed strong negative associations with mold damage. Overall, the identified stable loci and candidate lines provide foundations for effective molecular breeding of climate-resilient varieties. PLAIN LANGUAGE SUMMARYGrain mold is a fungal disease that reduces sorghum grain yield and quality, particularly in subhumid climates. With the limited number of resistant elite varieties, photoperiod-sensitive flowering to day length variation can contribute to grain mold escape at the end of rainy seasons. We characterized 286 sorghum recombinant inbred lines across three contrasting environments over two years along rainfall gradients in Senegal. Using flag leaf appearance (FLA), which is a photoperiodic flowering trait, strong genotype-environment interactions for FLA and genotypic plasticity were revealed. We identified and validated the common genomic locus associated with FLA variation and its plasticity across environments, the canonical maturity gene Ma1, which was influenced by temperature variation across environments. The presence of Ma1 in the background of photoperiod-sensitive lines enhances grain mold avoidance and yield stability along rainfall gradients in Senegal. CORE IDEASO_LIWe investigated photoperiodic flowering plasticity in sorghum as a contributor to grain mold resistance and yield stability along rainfall gradients. C_LIO_LIThe Maturity locus Ma1 (qFLA6.1) is the major contributor of photoperiodic flowering and its plasticity across semi-arid and subhumid environments. C_LIO_LIHybrid genotypes carrying two stable loci qFLA6.1 and qFLA6.2 sustain high grain mold avoidance in diverse environments. C_LIO_LIPhotoperiod-sensitive lines with medium to late flowering times are effective in avoiding grain mold, while maintaining yield stability in subhumid regions. C_LI

genetics↗

bioRxiv2025

Population genomic structure of sorghum landraces across landscape, environment and culture

The spread of staple crops to diverse environments over time and their current genetic structure may reflect historical dispersal by humans, sustained human preference for particular traits, and adaptation to local environments. Sorghum is a drought-tolerant crop native to Africa cultivated by hundreds of millions of smallholders globally. Here we examined the ecological context of population-genomic structure of 1,806 sorghum landraces across Africa and Eurasia to infer the relative contribution of environmental and cultural factors to sorghum genetic diversity across different relative time periods. Sorghum landraces were spatially and linguistically structured at a large-scale and within subregions, following a pattern of isolation by distance. Within regions, much of genomic structure was best explained by a mechanistic model of human travel time. In our assessment of hierarchical linguistic structure, we found that language families explain 4% of genomic variation while individual languages explain 13% of genomic variation, suggesting the importance of human culture and relationships in gene flow and selection. Variance partitioning showed that travel time, language, and climate explain up to 27% of genomic variation among landraces. We also observed regional differences in the degree of genetic relatedness across space and time in our assessment of shared ancestry. East Africa showed particularly strong geographic turnover in genomic composition and haplotype sharing, while West Africa showed substantial haplotype sharing even over large distances, signifying some rapidly spreading lineages. Thus, space, travel time, and culture likely capture important forces controlling sorghum genomic variation, but these factors operate heterogeneously over space.

plant biology↗

bioRxiv2025

Developing future resilience from signatures of adaptation across the sorghum pangenome

While the green revolution adapted a handful of crops to homogenous and high-input industrialized agriculture, much of the global population still relies on local food production from low-input smallholder farms that grow highly variable crop cultivars. The high diversity of the grain and bioenergy crop sorghum 1-4, and many other crops that were not homogenized during the green revolution 5, not only provides the raw materials for breeders to make substantial gains in cultivar improvement, but also constrains breeding efforts due to highly specialized locally adapted plant phenotypes 6. Here, we construct a 33-member pangenome and identify trait-associated variants in 1,988 cultivars and landraces. We then apply these resources to explore the complex interplay between historical contingency, ongoing adaptation, and the potential for future gains through climate-aware genome-enabled breeding. Specifically, our analyses conclusively demonstrate that multiple nested, deeply diverged, and previously uncharacterized structural variants in the domestication gene SHATTERING1 distinguish the previously established multicentric origin of sorghum. We then apply landscape genomics tests to reveal how gene flow, adaptation, and secondary contact created the complex genetic mosaic in current global breeding networks. Further analysis of climate-gene associations highlights candidate loci underlying adaptation, including the biosynthetic gene cluster for the cyanogenic glucoside dhurrin. Combined, the pangenome-informed variants developed here will enable both trait discovery and subsequent marker assays to accelerate breeding and provide a framework for similar applications in other diverse and non-model crops.

genomics↗

bioRxiv2025

Genomic approaches to build de novo elite breeding gene pools from locally-adapted landraces

Many nascent breeding programs aim to achieve genetic gain by crossing locally elite germplasm, but a lack of systematic approaches to develop elite gene pools from locally-adapted varieties hinders their progress. Motivated by the observation of undesirable transgressive segregation in presumed elite crosses in Senegalese cereal breeding programs, we designed approaches for de novo development of elite gene pools from locally-adapted landrace-derived germplasm. We first define two types of "elite" germplasm: cis-elite, phenotypically similar and genetically homogeneous for locally-adapted traits ("acquired traits"); versus trans-elite, phenotypically similar, but genetically heterogeneous for acquired traits. Next, we defined two genomic approaches for de novo inference of elite gene pools: population-based genotypic inference (PGI) and QTL-based genotypic inference (QGI), and compared to a family-based phenotypic inference (FPI) approach. Using simulations that trace the evolution from locally-adapted landraces to elite breeding lines, we evaluate the effectiveness of these strategies in nascent forward breeding programs. QGI accurately and cost-effectively identifies both cis- and trans-elite pairs, regardless of the underlying trait architecture, while PGI is less sensitive when trait architecture is oligogenic. Over ten cycles of phenotypic recurrent selection, programs based on cis-elite crosses consistently outperformed those based on trans-elite crosses for genetic gain. The findings highlight the value of trait genetic architecture knowledge for elite gene pool development and provide a practical roadmap for elite germplasm development in modernizing breeding programs.

genetics↗

bioRxiv2025

Interchromosomal Linkage Disequilibrium Analysis Reveals Strong Indications of Sign Epistasis in Wheat Breeding Families

Additive gene action is assumed to underly quantitative traits, but the eventual poor performance of elite wheat lines as parents suggests that epistasis could be the underlying genetic architecture. Sign epistasis is characterized by alleles having either a beneficial or detrimental effect depending on the genetic background, which can result in elite lines that fail as parents in certain parental combinations. Hence, the objective of this study were to test the existence of sign epistasis and examine its consequences to wheat breeding. The presence of sign epistasis is expected to distort the allele frequency distribution between two interacting genes compared to neutral sites, creating strong linkage disequilibrium (LD). To test this hypothesis, analysis of interchromosomal LD in breeding families was performed and detected 19 regions in strong disequilibrium, whose allele frequency distribution matched the sign epistasis prediction and falsified the competing hypothesis of additive selection. To validate these candidate interactions while avoiding the biases of a circular analysis and the confounding effects of genetic drift, two independent sets of populations were analyzed. Genetic drift was attributed to creating the sign epistasis patterns observed in eleven interactions, but there was not sufficient evidence to reject the sign epistasis hypothesis in eight interactions. Sign epistasis may explain the poor performance of elite lines as parents, as crossing lines with complementary allelic combination re-establishes epistatic variance in the offspring. Reduction in the effective population size in certain crosses may also occur when unfavorable sign epistatic combinations are deleterious. The potential existence of di-genic and higher order epistatic interactions in elite germplasm can tremendously impact breeding strategies as managing epistasis becomes imperative for success.

genetics↗

bioRxiv2025

Ancient pangenomic origins of noncanonical NLR genes underlying the recent evolutionary rescue of a staple crop

Evolutionary rescue occurs when populations in deteriorating environments avoid extinction by rapid adaptation. The recent evolutionary rescue of the cereal crop sorghum via RMES1 aphid resistance is among a few known in situ cases, but its pangenomic origins and molecular basis is not yet known. Here, we describe the behavioral effects, molecular endophenotypes, and pangenomic evolution underlying this evolutionary rescue. Analysis of near-isogenic lines show that RMES1 disrupts phloem feeding via global immunity activation of conserved defense networks. A growth-to-defense transition is evidenced by extensive transcriptome remodeling (>15% of expressed genes) and mediated by salicylic acid signaling. Nucleotide-binding leucine-rich repeat (NLR) immune receptor genes at the RMES1 locus harbored on a large tandem duplication have extensive copy number variation across the sorghum pangenome. The likely causative NLRs (RMES1A and RMES1B) were inferred from expression and structural variation. The NLRs encoded at RMES1 lack an N-terminal signaling domain and have nucleotide-binding domain sequence variation expected to result in a loss of ATP binding, suggesting RMES1 NLRs function via a noncanonical mechanism. The RMES1 NLR family is shared across the grass super-pangenome and includes the brown planthopper resistance gene BPH40 in Oryza sativa, which is syntenic to RMES1. Finally, k-mer analysis of RMES1 haplotypes in the sorghum pangenome established the East African origin of rare standing variation for resistance. Thus, the birth-and-death process at an ancient gene cluster generated pangenomic variation that was recruited to activate coordinated defense pathways and provide evolutionary rescue.

genetics↗

bioRxiv2024

Loss of pleiotropic regulatory functions in Tannin1, the sorghum ortholog of Arabidopsis master regulator TTG1

Transcriptional master regulators are often targeted to improve plant traits, but antagonistic pleiotropic effects of these regulators can hamper this approach. The Myb-bHLH-WDR (MBW) complex is a broadly-conserved transcriptional regulator affecting pigmentation, biotic stress resistance, and abiotic stress tolerance. We investigated the function of sorghum grain pigmentation regulator Tannin1, the ortholog of Arabidopsis pleiotropic WD40 regulator TTG1, to test for conserved pleiotropic regulatory effects and to better understand the evolution of the MBW complex in Poaceae. We characterized genome-wide differential expression of leaf tissue using RNA sequencing in near-isogenic lines (NILs) that contrasted wildtype Tan1 and loss-of-function tan1-b alleles, under optimal temperature and chilling stress. Notably, Gene Ontology analyses revealed no pathways with differential expression between Tan1 and tan1-b NILs, suggesting that, in contrast to Arabidopsis TTG1, Tannin1 has no pleiotropic regulatory role in leaves. Further, NILs had no visible difference in anthocyanin pigmentation, and no genes with known or expected function in flavonoid synthesis were differentially expressed. Genome-wide, only 18 total genes were differentially expressed between NILs, with six of these genes located inside the NIL introgression region, an observation most parsimoniously explained by cis-regulatory effects unrelated to Tannin1 regulation. Comparing our findings with known function of TTG1 orthologs in maize, rice, and Arabidopsis, we conclude that pleiotropic regulatory function in leaf tissue was likely lost in panicoid grass evolution before the sorghum-maize split. These findings inform future molecular breeding of MBW regulated traits and highlight the benefit of subfunctionalization to relieve pleiotropic constraints.

plant biology↗

bioRxiv2024

Evolutionary fingerprint in rodent PD1 confers weakened activity and enhanced tumor immunity compared to human PD1

Mechanistic understanding of the immune checkpoint receptor PD1 is largely based on mouse models, but human and mouse PD1 orthologs exhibit only 59.6% identity in amino acid sequences. Here we show that human PD1 is more inhibitory than mouse PD1 due to stronger interactions with the ligands PDL1 and PDL2 and with the effector phosphatase Shp2. A novel motif highly conserved among PD1 orthologs in vertebrates except in rodents is primarily responsible for the differential Shp2 recruitment. Evolutionary analysis suggested that rodent PD1 orthologs uniquely underwent functional relaxation, particularly during the K-Pg boundary. Humanization of the PD1 intracellular domain disrupted the anti-tumor activity of mouse T cells while increasing the magnitude of anti-PD1 response. Together, our study uncovers species-specific features of the PD1 pathway, with implications to PD1 evolution and differential anti-PD(L)1 responses in mouse models and human patients.

immunology↗

bioRxiv2024

An extended omnigenic model explains genome-phenome relationships for complex traits in global sorghum diversity

A central finding of complex trait genetics is the geometric distribution of effect sizes, but the biological basis of this phenomena is not understood. The omnigenic model (OM) could explain this architecture, with oligogenic variation arising from direct regulatory genes (core genes) and polygenic variation from indirect regulators (peripheral trans regulators). Plant yield is a canonical complex trait and here we tested the OM using genome-phenome analysis of biomass yield in global sorghum diversity. We used field-based phenomics to characterize dynamic growth and yield formation traits, then decomposed oligogenic and polygenic components of variation using genome-wide association studies (GWAS), genome-wide prediction (GWP), and tissue-specific transcriptome analyses. We identified major dynamic QTL, including several persistent (Dw1, Dw3) or transient (ELF3) QTL at known genes, consistent with the oligogenic-core of the OM. Next, we evaluated a key prediction on the peripheral-polygenic component - a positive correlation between GWP marker loadings and gene expression in relevant tissues. GWP loadings are indeed correlated with gene expression in relevant tissues. However, correlations are often higher with non-relevant tissues from earlier growth stages or tissues, which is not predicted by within-tissue trans regulation for the peripheral-polygenic component (the "omnigenic in space" model). Therefore, these findings suggest that genes expressed in early growth stages, with indirect effects on later traits, are contributing to polygenic variation ("omnigenic in time"). Together, our findings suggest that an extended OM, with regulatory effects both in space and in time, could explain the ubiquitous geometric genetic architecture of complex traits.

genetics↗

bioRxiv2024

Improving genomic selection in hexaploid wheat with sub-genome additive and epistatic models

The goal of wheat breeding is the development of superior cultivars tailored to specific environments, and the identification of promising crosses is crucial for the success of breeding programs. Although genomic estimated breeding values were developed to estimate additive effects of genotypes before testing as parents, application has focused on predicting performance of candidate lines, ignoring non-additive genetic effects. However, non-additive genetic effects are hypothesized to be especially importance in allopolyploid species due to the interaction between homeologous genes. The objectives of this study were to model additive and additive-by-additive epistatic effects to better delineate the genetic architecture of grain yield in wheat and to the improve accuracy of genomewide predictions. The dataset utilized consisted of 3740 F5:6 experimental lines tested in the K-State wheat breeding program across the years 2016 and 2018. Covariance matrices were calculated based on whole and sub-genome marker data and the natural and orthogonal interaction approach (NOIA) was used to estimate variance components for additive and additive-by-additive epistatic effects. Incorporating epistatic effects in additive models resulted in non-orthogonal partitioning of genetic effects but increased total genetic variance and reduced deviance information criteria. Estimation of sub-genome effects indicated that genotypes with the greatest whole genome effects often combine sub-genomes with intermediate to high effects, suggesting potential for crossing parental lines which have complementary sub-genome effects. Modeling epistasis in either whole-genome or sub-genome models led to a marginal (3%) but significant improvement in genomic prediction accuracy, which could result in significant genetic gains across multiple cycles of breeding.

genetics↗

bioRxiv2024

Rapamycin Treatment Reduces Brain Pericyte Constriction in Ischemic Stroke

The contraction and subsequent death of brain pericytes may play a role in microvascular no-reflow following the re-opening of an occluded artery during ischemic stroke. Mammalian target of rapamycin (mTOR) inhibition has been shown to reduce motility/contractility of various cancer cell lines and reduce neuronal cell death in stroke. However, the effects of mTOR inhibition on brain pericyte contraction and death during ischemia have not yet been investigated. Cultured pericytes exposed to simulated ischemia for 12 hours in vitro contracted after less than 1 h, which was about 7h prior to cell death. Rapamycin significantly reduced the rate of pericyte contraction during ischemia, however, it did not have a significant effect on pericyte viability at any time point. Rapamycin appeared to reduce pericyte contraction through a RhoA-dependent pathway, independent of changes in intracellular calcium. Using a mouse model of middle cerebral artery occlusion, rapamycin significantly increased the diameter of capillaries underneath pericytes and increased the number of open capillaries 30 minutes following recanalization. Our findings suggest rapamycin may be a useful adjuvant therapeutic to reduce pericyte contraction and improve cerebral reperfusion post-stroke.

neuroscience↗

bioRxiv2024

Microglia contact cerebral vasculature through gaps between astrocyte endfeet

The close spatial relationship between microglia and cerebral blood vessels implicates microglia in vascular development, homeostasis and disease. In this study we used the publicly available Cortical MM^3 electron microscopy dataset to systematically investigate microglial interactions with the vasculature. Our analysis revealed that approximately 20% of microglia formed direct contacts with blood vessels through gaps between adjacent astrocyte endfeet. We termed these contact points "plugs". Plug-forming microglia exhibited closer proximity to blood vessels than non-plug forming microglia and formed multiple plugs, predominantly near the soma, ranging in surface area from [~]0.01 m2 to [~]15 m2. Plugs were enriched at the venule end of the vascular tree and displayed a preference for contacting endothelial cells over pericytes at a ratio of 3:1. In summary, we provide novel insights into the ultrastructural relationship between microglia and the vasculature, laying a foundation for understanding how these contacts contribute to the functional cross-talk between microglia and cells of the vasculature in health and disease.

neuroscience↗

bioRxiv2023

Globally-deployed sorghum aphid resistance gene RMES1 is vulnerable to biotype shifts but being bolstered by RMES2

Durable host plant resistance (HPR) to insect pests is critical for sustainable agriculture. Natural variation exists for aphid HPR in sorghum (Sorghum bicolor) but the genetic architecture and phenotype has not been clarified for most sources. To assess the threat of a sorghum aphid (Melanaphis sorghi) biotype shift, we characterized the phenotype of Resistance to Melanaphis sorghi 1 (RMES1) and contributing HPR architecture in globally-admixed populations selected under severe aphid infestation in Haiti. We found RMES1 reduces sorghum aphid fecundity but not bird cherry-oat aphid (Rhopalosiphum padi) fecundity, suggesting a discriminant HPR response typical of gene-for-gene interaction. A second resistant gene, RMES2, were more frequent than RMES1 resistant alleles in landraces and historic breeding lines. RMES2 contributes early and mid-season aphid resistance in a segregating F2 population, however RMES1 was only significant with mid-season fitness. In a fixed population with high aphid resistance, RMES1 and RMES2 were selected for demonstrating a lack of significant antagonistic pleiotropy. Associations with resistance co-located with cyanogenic glucoside biosynthesis genes support additional HPR sources. Globally, therefore, a vulnerable HPR source (RMES1) is bolstered by a second common source of resistance in breeding programs (RMES2) which may be staving off a biotype shift. HIGHLIGHTThe globally-deployed sorghum aphid resistance gene, RMES1, reduces aphid reproduction and therefore is vulnerable to a biotype shift. A second major gene, RMES2, and cyanogenesis may increase global durability of resistance.

plant biology↗

bioRxiv2023

Pericyte ablation causes hypoactivity and reactive gliosis in adult mice

Pericytes are contractile cells that enwrap capillaries allowing them to control blood flow, maintain the blood-brain barrier and regulate immune cell trafficking in the CNS. Pericytes are lost or become dysfunctional in neurodegenerative diseases such as Alzheimers disease, stroke, and multiple sclerosis, but their role in health and disease is poorly understood. Our aim was to evaluate blood-brain barrier integrity and glial reactivity, and to assess behavioural phenotypes that emerge following pericyte ablation in adult mice. The delivery of tamoxifen to PDGFR{beta}-CreERT2 :: Rosa26-DTA transgenic mice produced a dose-dependent ablation of pericytes. A single low dose of tamoxifen ablated approximately half of all brain pericytes, and two consecutive daily high doses ablated more than 80% of brain pericytes. To determine whether pericyte ablation could induce a behavioural phenotype, we assessed patterns of voluntary movement, as well as balance and coordination using the open field and beam walk tasks. Mice with [~]50% pericyte loss travelled half the distance and spent half as much time moving in the open field as control mice. Mice with more than 80% pericyte ablation also slipped more frequently in the beam walk task than control mice. In brain cryosections from pericyte-ablated mice, blood vessel structure was unchanged, but lumen area was increased. Pericyte-ablated mice also experienced blood-brain barrier leakage, hypoxia and increased microgliosis and astrogliosis compared to control mice. Our results highlight the importance of pericytes for brain health, as pericyte loss can directly drive brain injury and behavioural alterations in mice.

neuroscience↗