Biology subjects

Anderson, J. A.

Publications and source records attributed to Anderson, J. A..

14 recordsLinked to original sources

bioRxiv2025

A century of breeding has preserved genetic variation, accumulated favorable alleles, and shaped the Rht gene portfolio in North American spring wheat

Hard red spring wheat (HRSW) is an important market class of wheat in North America with a rich history of breeding. We genotyped 1,013 HRSW lines representing a century of breeding material using a SNP array and targeted KASP genotyping to assess the changes in genetic diversity and Rht genes in HRSW from North America. Results show that early breeding efforts broadened an initially narrow gene pool derived from a few founders and subsequently maintained the genetic diversity. Analysis of Rht genes revealed that Rht-D1b was the predominant semi-dwarf allele from introduction of the Green Revolution genes (Rht-B1 and Rht-D1) in 1960s until the FHB epidemics of 1990s, when most breeding programs shifted to Rht-B1b. However, adoption of Rht-B1b and Rht-D1b remains low in some regions of the Great Plains. The dwarf alleles at GA-sensitive Rht24 and Rht25 have persisted in the region at low frequencies before the introduction of Green Revolution genes and have increased in frequency in recent decades. We also analyzed the effect of Rht genes on plant height (PH) in the HRSW growing region and found that Rht-B1b or Rht-D1b results in [~]12% reduction in PH, which decreases to [~]9% in dry environments. Notably, combining dwarfing alleles at Rht24 and Rht25 reduced height by [~]6% in dry environments, suggesting an alternative approach for reducing PH. Our analysis also revealed significant genetic interactions between Rht-B1 and Rht25, as well as between Rht-D1 and Rht24, which could help fine-tune PH for different environments by employing appropriate Rht combinations. Furthermore, our results demonstrate positive selection for photoperiod sensitivity in recent decades, particularly in high-latitude regions. This study provides a valuable genomic resource, and the findings enhance our understanding of past breeding efforts while offering insights to guide future plant breeding strategies.

plant biology↗

bioRxiv2025

Genetically-based sperm discrimination in the vaginal tract of a primate species

Females influence offspring paternity through diverse pre- and post-copulatory mechanisms. Sperm discrimination--the differential physiological response to ejaculates based on male or sperm characteristics--can bias fertilization outcomes, but in vivo evidence of this process in large-bodied mammals is lacking. Here, we tested whether two aspects of female physiology that affect sperm survival-vaginal immune response and pH-are modulated by male genetic makeup in a nonhuman primate. We observed post-copulatory differences in vaginal gene expression and pH, with the strongest immune responses and largest pH decreases, harmful to sperm, exhibited by females mating with genetically similar males. These findings support genetically based post-copulatory mate discrimination in primates, shedding light on the interaction between male gametes and the female reproductive tract and potentially explaining variation in conception probability.

evolutionary biology↗

bioRxiv2025

Admixture influences the genetic architecture of DNA methylation in a wild primate hybrid zone

BackgroundHybrid zones play a central role in evolutionary biology because they serve as natural laboratories for studying how traits and taxa diverge. Changes in gene regulation make important contributions to this process. However, the degree to which admixture shapes gene regulatory variation in hybrid populations remains poorly understood. Here, we combine genome-wide resequencing and DNA methylation data from 295 hybrid baboons--members of a single, intensively studied natural population--to investigate how admixture affects the genetic architecture of this important epigenetic mark. ResultsWe find that local genetic ancestry frequently predicts DNA methylation levels and recapitulates differences between the parent species. By performing methylation quantitative trait locus (meQTL) mapping, we show that these differences predominantly arise due to evolved differences in allele frequencies. Thus, admixture in the hybrid population increases variance in DNA methylation, including by introducing meQTL that would otherwise be invariant. Finally, we integrate massively parallel reporter assay data to show that admixture-derived variation in DNA methylation alters enhancer activity and gene expression. ConclusionsTogether, these results demonstrate how admixture can meaningfully alter the genetic architecture of gene regulatory traits in natural hybrid zones. They also suggest that the genetic architecture of DNA methylation is conserved across closely related primates, suggesting that genetic effects on gene regulation may remain stable over timescales that range into the millions of years.

evolutionary biology↗

bioRxiv2025

Genetic Gains from Sixty Years of Spring Wheat Breeding in the Northern Plains of the US

Evaluating genetic gains over time is essential for assessing the success of breeding programs and refining strategies for ongoing improvement. Hard red spring (HRS) wheat is an important wheat class in the US and is primarily grown in the Northern Great Plains. Despite a long history of breeding efforts in this region, long-term quantification of genetic gains for key traits has remained limited. This study analyzes over sixty years of data from the USDA-coordinated Hard Red Spring Wheat Uniform Regional Nursery (HRSWURN) to evaluate genetic advancements in agronomic traits across multiple phases. A significant positive genetic gain of 0.61% per annum was observed for grain yield in HRS wheat released in the Northern US region, which is lower than the expected gains needed to meet future wheat demand. The change was 0.07% for test weight, -0.04% for days to heading, and -0.16% for plant height. Notably, sustained yield improvements have not affected grain protein levels since they were first measured in 1995, indicating that ongoing selection has effectively balanced grain yield and protein despite their negative correlation (r = -0.31). Assessment of genetic gains over 20-year phases suggested slowing rates of genetic gains for grain yield but did not indicate any plateaus. The realized genetic gains were generally higher for individual breeding programs when breeding for target environments, with the public breeding program in Minnesota observing gains of approximately 1% per annum. These findings highlight the significant impact of long-term breeding efforts and offer valuable insights for refining future breeding strategies.

plant biology↗

bioRxiv2024

Enhancing student comprehension of paternity assignment in molecular primatology: a pilot study using a Shiny web application in Kenya

Kinship is a major determinant of affiliative and mating behavior in primates. In field studies, identifying kin typically relies in part on genetic analysis, especially for discriminating paternal relationships. Such analyses assume knowledge of Mendelian inheritance, genotyping technologies, and basic statistical inference. Consequently, they can be difficult for students to grasp, particularly through traditional lecture formats. Here, we investigate whether integrating an additional active learning approach--interaction with a Shiny web application, DadApp, which implements a popular paternity inference approach in an accessible graphical user interface--improves student understanding of genetic kinship analysis in molecular primatology. We do so in the context of a non-traditional learning environment in Kenya, a developing nation in which students have limited access to technology, and where the efficacy of educational Shiny apps has never been assessed. Twenty-eight (28) participants with diverse educational backgrounds attended an introductory lecture on genetics and paternity inference, completed a pre-test, interacted with DadApp via a structured set of exercises and questions, and then completed a post-test and survey about their experience and subjective understanding. Post-test scores significantly improved relative to pre-test scores (p-value=3.75 x 10-6 . Further, student interest and confidence in the subject matter significantly increased after the practical session with DadApp. Our results suggest that Shiny web app-based active learning approaches have potential benefits in communicating complex topics in molecular primatology, including in resource-limited settings where such methods have not yet experienced high penetrance. Graphical Abstract*Images in the graphical abstract are courtesy of publicdomainpictures.net O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/610690v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@5ce036org.highwire.dtl.DTLVardef@18429a0org.highwire.dtl.DTLVardef@1c8d997org.highwire.dtl.DTLVardef@1456624_HPS_FORMAT_FIGEXP M_FIG C_FIG

scientific communication and education↗

bioRxiv2023

An RGB based deep neural network for high fidelity Fusarium head blight phenotyping in wheat

Fusarium head blight (FHB) in wheat is an economically important disease, which can cause yield losses exceeding 50% and the causal pathogen that infects spikes produces harmful mycotoxins. Breeding for host resistance remains the most effective disease control method; but time, labor, and human subjectivity during disease scoring limits selection advancements. In this study we describe an innovative, high-throughput phenotyping rover for capturing in-field RGB images and a deep neural network pipeline for wheat spike detection and FHB disease quantification. The image analysis pipeline successfully detects wheat spikes from images under variable field conditions, segments spikes and diseased tissue in the spikes, and quantifies disease severity as the region of intersection between spike and disease masks. Model inferences on an individual spike and plot basis were compared to human visual disease scoring in the field and on imagery for model evaluation. The precision and throughput of the model surpassed traditional field rating methods. The accuracy of FHB severity assessments of the model was equivalent to human disease annotations of images, however individual spike disease assessment was influenced by field location. The model was able to quantify FHB in images taken with different camera orientations in an unseen year, which demonstrates strong generalizability. This innovative pipeline represents a breakthrough in FHB phenotyping, offering precise and efficient assessment of FHB on both individual spikes and plot aggregates. The model is robust to different conditions and the potential to standardize disease evaluation methods across the community make it a valuable tool for studying and managing this economically significant fungal disease.

plant biology↗

bioRxiv2023

DNA methylation signatures of early life adversity are exposure-dependent in wild baboons

The early life environment can profoundly shape the trajectory of an animals life, even years or decades later. One mechanism proposed to contribute to these early life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early life effects on fitness-related traits. Significance statementThe environment animals face when young can affect how they function throughout life. Long-lasting changes in DNA methylation--a chemical mark deposited on DNA that can affect gene activity--have been hypothesized to contribute to early life effects. But evidence for persistent, early environment-associated differences in DNA methylation is lacking in wild animals. Here, we show that early life adversity in wild baboons predicts DNA methylation levels in adulthood, especially for animals born in low resource environments and drought conditions. We also show that some of the changes we observe in DNA methylation have the capacity to influence gene activity levels. Together, our results support the idea that early experiences can become biologically embedded in the genomes of wild animals.

genomics↗

bioRxiv2023

Hypoxia-inducible factor 2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency

Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations in SLC30A10 are the first known inherited cause of manganese excess. SLC30A10 is an apical membrane transport protein that exports manganese from hepatocytes into bile and from enterocytes into the lumen of the gastrointestinal tract. SLC30A10 deficiency results in impaired gastrointestinal manganese excretion, leading to severe manganese excess, neurologic deficits, liver cirrhosis, polycythemia, and erythropoietin excess. Neurologic and liver disease are attributed to manganese toxicity. Polycythemia is attributed to erythropoietin excess, but the basis of erythropoietin excess in SLC30A10 deficiency has yet to be established. Here we demonstrate that erythropoietin expression is increased in liver but decreased in kidneys in Slc30a10-deficient mice. Using pharmacologic and genetic approaches, we show that liver expression of hypoxia-inducible factor 2 (Hif2), a transcription factor that mediates the cellular response to hypoxia, is essential for erythropoietin excess and polycythemia in Slc30a10-deficient mice, while hypoxia-inducible factor 1 (HIF1) plays no discernible role. RNA-seq analysis determined that Slc30a10-deficient livers exhibit aberrant expression of a large number of genes, most of which align with cell cycle and metabolic processes, while hepatic Hif2 deficiency attenuates differential expression of half of these genes in mutant mice. One such gene downregulated in Slc30a10-deficient mice in a Hif2-dependent manner is hepcidin, a hormonal inhibitor of dietary iron absorption. Our analyses indicate that hepcidin downregulation serves to increase iron absorption to meet the demands of erythropoiesis driven by erythropoietin excess. Finally, we also observed that hepatic Hif2 deficiency attenuates tissue manganese excess, although the underlying cause of this observation is not clear at this time. Overall, our results indicate that HIF2 is a key determinant of pathophysiology in SLC30A10 deficiency. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=148 HEIGHT=200 SRC="FIGDIR/small/529270v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@c25fc8org.highwire.dtl.DTLVardef@11e70feorg.highwire.dtl.DTLVardef@18c5518org.highwire.dtl.DTLVardef@26b61f_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2021

Selection against admixture and gene regulatory divergence in a long-term primate field study

Admixture has profoundly influenced evolution across the tree of life, including in humans and other primates1,2. However, we have limited insight into the genetic and phenotypic consequences of admixture in primates, especially during its key early stages. Here, we address this gap by combining 50 years of field observations with population and functional genomic data from yellow (Papio cynocephalus) and anubis (P. anubis) baboons in Kenya, in a longitudinally studied population that has experienced both historical and recent admixture3. We use whole-genome sequencing to characterize the extent of the hybrid zone, estimate local ancestry for 442 known individuals, and predict the landscape of introgression across the genome. Despite no major fitness costs to hybrids, we identify signatures of selection against introgression that are strikingly similar to those described for archaic hominins4-6. These signatures are strongest near loci with large ancestry effects on gene expression, supporting the importance of gene regulation in primate evolution and the idea that selection targeted large regulatory effects following archaic hominin admixture7,8. Our results show that genomic data and field observations of hybrids are important and mutually informative. They therefore demonstrate the value of other primates as living models for phenomena that we cannot observe in our own lineage.

evolutionary biology↗

bioRxiv2021

Chromosome-level Thlaspi arvense genome provides new tools for translational research and for a newly domesticated cash cover crop of the cooler climates

Thlaspi arvense (field pennycress) is being domesticated as a winter annual oilseed crop capable of improving ecosystems and intensifying agricultural productivity without increasing land use. It is a selfing diploid with a short life cycle and is amenable to genetic manipulations, making it an accessible field-based model species for genetics and epigenetics. The availability of a high quality reference genome is vital for understanding pennycress physiology and for clarifying its evolutionary history within the Brassicaceae. Here, we present a chromosome-level genome assembly of var. MN106-Ref with improved gene annotation, and use it to investigate gene structure differences between two accessions (MN108 and Spring32-10) that are highly amenable to genetic transformation. We describe small RNAs, pseudogenes, and transposable elements, and highlight tissue specific expression and methylation patterns. Resequencing of forty wild accessions provides insights into genome-wide genetic variation as well as QTL regions for flowering time and a seedling color phenotype. Altogether, these data will serve as a tool for pennycress improvement in general and for translational research across the Brassicaceae.

plant biology↗

bioRxiv2020

Visuomotor Activation of Inhibition-Processing in Pediatric Obsessive Compulsive Disorder: A Magnetoencephalography Study

BackgroundThe ability to inhibit a response is a component of executive control that is impaired in many individuals with obsessive compulsive disorder (OCD) and may contribute to clinical symptoms. This study explored whether neural processing during response inhibition, measured using magnetoencephalography (MEG), differed in a sample of medication-naive youth with OCD, compared to typically developing controls (TDC). MethodsData was acquired from 20 medication-naive children and youth with OCD (11.9 {+/-} 2.1 SD years) and 14 TDC (12.3 {+/-} 2.1 SD years). MEG was used to localize and characterize neural activity during a Go/No-Go task. Regional differences in amplitude of activity during a Go and No-Go condition between OCD versus TDC were examined. ResultsIn response to the visual cue presented during the Go condition, participants with OCD showed significantly increased amplitude of activity in the primary motor (MI) cortex compared to TDC. A trend towards decreased amplitude of activity in the orbitofrontal cortex in OCD versus TDC was also found during stop errors in the No-Go condition. ConclusionOur preliminary study in a small medication-naive sample suggests that neural response within motor and orbitofrontal regions may be altered during Go/No-Go Task performance, and that MEG as an imaging tool may be sensitive to detecting such differences.

neuroscience↗

bioRxiv2019

Progress toward the identification and stacking of crucial domestication traits in pennycress

The oilseed species Thlaspi arvense (pennycress) is being domesticated as a new crop that can provide both important ecosystem services and intensify farmland output. Through the use of high throughput sequencing and phenotyping, along with classical mutagenesis key traits needed for pennycress domestication have been identified. Domestication traits identified herein include reduced pod shatter, early maturity, reduced seed glucosinolate levels, and improved oil fatty acid content. By taking advantage of pennycress close genetic relationship with Arabidopsis thaliana, the causative mutations responsible for each of these traits have been identified. These mutations have been used to develop molecular markers to begin to stack the traits into individual lines.

plant biology↗

bioRxiv2019

VarSight: Prioritizing Clinically Reported Variants with Binary Classification Algorithms

MotivationIn genomic medicine for rare disease patients, the primary goal is to identify one or more variants that cause their disease. Typically, this is done through filtering and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance. ResultsWe tested the application of classification algorithms that ingest variant predictions along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network. We treated the classifiers as variant prioritization systems and compared them to another variant prioritization algorithm and two single-measure controls. We showed that these classifiers outperformed the other methods with the best classifier ranking 73% of all reported variants and 97% of reported pathogenic variants in the top 20. AvailabilityThe scripts used to generate results presented in this paper are available at https://github.com/HudsonAlpha/VarSight. Contactjholt@hudsonalpha.org

bioinformatics↗

bioRxiv2017

Conservation of specificity in two low-specificity proteins

S100 proteins bind linear peptide regions of target proteins and modulate their activity. The peptide binding interface, however, has remarkably low specificity and can interact with many target peptides. It is not clear if the interface discriminates targets in a biological context, or whether biological specificity is achieved exclusively through external factors such as subcellular localization. To discriminate these possibilities, we used an evolutionary biochemical approach to trace the evolution of paralogs S100A5 and S100A6. We first used isothermal titration calorimetry to study the binding of a collection of peptides with diverse sequence, hydrophobicity, and charge to human S100A5 and S100A6. These proteins bound distinct, but overlapping, sets of peptide targets. We then studied the peptide binding properties of S100A5 and S100A6 orthologs sampled from across five representative amniote species. We found that the pattern of binding specificity was conserved along all lineages, for the last 320 million years, despite the low specificity of each protein. We next used Ancestral Sequence Reconstruction to determine the binding specificity of the last common ancestor of the paralogs. We found the ancestor bound the whole set of peptides bound by modern S100A5 and S100A6 proteins, suggesting that paralog specificity evolved by subfunctionalization. To rule out the possibility that specificity is conserved because it is difficult to modify, we identified a single historical mutation that, when reverted in human S100A5, gave it the ability to bind an S100A6-specific peptide. These results indicate that there are strong evolutionary constraints on peptide binding specificity, and that, despite being able to bind a large number of targets, the specificity of S100 peptide interfaces is indeed important for the biology of these proteins.

biochemistry↗