Biology subjects

Beck, E. A.

Publications and source records attributed to Beck, E. A..

8 recordsLinked to original sources

bioRxiv2026

Assessing positive selection in centromere-associated kinetochore proteins across Metazoan groups.

Centromeres are comprised of long stretches of repetitive DNA that evolve rapidly in organisms across the tree of life. Consistent selfish centromere evolution can also have cascading effects - driving rapid evolution in interacting kinetochore proteins - possibly to maintain centromere-kinetochore compatibility. Effects of selfishly evolving centromeres on interacting proteins are most heavily studied in the inner kinetochore and assembly proteins including the constitutive centromere-associated network proteins CENP-A and CENP-C with some exploration of the extended effects to other kinetochore-associated protein complexes. While rapid evolution of the centromere has been broadly studied in many organisms, studies assessing positive selection in centromere-associated kinetochore proteins have largely focused on Drosophila. Here, we tested the hypothesis that signatures of positive selection would be present in outer kinetochore and condensin genes in diverse animal groups. We selected two protein complexes -the Condensin I complex and the Mis12 Complex - to test for positive selection in parasitic wasps, two groups of ray-finned fishes (including the amazon molly an asexual diploid exempt from centromere drive), and two groups of primates. We did not find selection using any test in any protein in the amazon molly but did find sporadic positive selection in proteins in both complexes across all groups.

evolutionary biology↗

bioRxiv2025

Spontaneous mutant in threespine stickleback connects endosome trafficking disorders and inflammatory bowel diseases via changes in the gut microbiome

Endosomes are organelles that sort and traffic materials to different cellular compartments to enable performance of other organelles. One group of organelles supported by endosomes are lysosome related organelles (LROs) - which perform specialized functions using endocytosed or recycled materials from endosomes. LROs include melanosomes, lytic granules, platelet dense granules, lamellar bodies, and more. Individuals with endosome trafficking disorders commonly present with oculocutaneous albinism due to insufficient trafficking to - and maturation of - melanosomes. While the loss of pigment is an easily identifiable phenotype, mutations in endosome trafficking can also cause multi-organ system symptoms due to more broad disruption of LROs. Different endosome trafficking mutations impact LRO maturation at different degrees of severity and can impact a subset or all LROs leading to a wide range of symptomologies. Endosome trafficking disorders can present with oculocutaneous albinism (caused by mutated melanosomes), blood diathesis (caused by mutated platelet dense granules), pulmonary fibrosis (caused by mutated lamellar bodies), or chronic inflammation and inflammatory bowel disease (IBD) (caused by mutated lytic granules), as well as other symptoms. The shared inflammatory patterns of Hermansky-Pudlak Syndrome (HPS) and Inflammatory Bowel Disease (IBD) are well studied. However, impacts of this shared gastrointestinal inflammation on the gut microbiome remain unexplored. Using a spontaneously identified mutant family of threespine stickleback fish, we characterize changes in LROs and symptoms of oculocutaneous albinism. We further demonstrate that the shared gastrointestinal phenotypes of HPS and IBD extend to the gut microbiome showing similar shifts in microbial communities consistent with IBD. We argue endosome trafficking models should be explored as models to study the gut microbiome in addition to inflammatory phenotypes in IBD, and importantly, be used to test microbial/dietary interventions for both IBD and endosome trafficking disorders.

genetics↗

bioRxiv2024

Maternal Western-style diet programs skeletal muscle gene expression in lean adolescent Japanese macaque offspring

Early-life exposure to maternal obesity or a maternal calorically dense Western-style diet (WSD) is strongly associated with a greater risk of metabolic diseases in offspring, most notably insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). Prior studies in our well-characterized Japanese macaque model demonstrated that offspring of dams fed a WSD, even when weaned onto a control (CTR) diet, had reductions in skeletal muscle mitochondrial metabolism and increased skeletal muscle insulin resistance compared to offspring of dams on CTR diet. In the current study, we employed a nested design to test for differences in gene expression in skeletal muscle from lean 3-year-old adolescent offspring from dams fed a maternal WSD in both the presence and absence of maternal obesity or lean dams fed a CTR diet. We included offspring weaned to both a WSD or CTR diet to further account for differences in response to post-weaning diet and interaction effects between diets. Overall, we found that a maternal WSD fed to dams during pregnancy and lactation was the principal driver of differential gene expression (DEG) in offspring muscle at this time point. We identified key gene pathways important in insulin signaling including PI3K-Akt and MAP-kinase, regulation of muscle regeneration, and transcription-translation feedback loops, in both male and female offspring. Muscle DEG showed no measurable difference between offspring of obese dams on WSD compared to those of lean dams fed WSD. A post-weaning WSD effected offspring transcription only in individuals from the maternal CTR diet group but not in maternal WSD group. Collectively, we identify that maternal diet composition has a significant and lasting impact on offspring muscle transcriptome and influences later transcriptional response to WSD in muscle, which may underlie the increased metabolic disease risk in offspring.

physiology↗

bioRxiv2022

Host genomic variation shapes gut microbiome diversity in threespine stickleback fish

Variation among host-associated microbiomes is well documented across species, populations, and individuals. However, the relative importance of host genetic differences for microbiome variation has been difficult to study. While research in humans has shown that genetic variation influences microbiome differences, confounding environmental effects have been very difficult to control. Isogenic laboratory models help isolate host genetic variants to test for influences of the environment or large-effect mutations on the microbiome, but such studies seldom incorporate natural genetic variation. Thus, although many important factors potentially impacting the microbiome have been identified, most studies have failed to test for the direct influence of natural host-genetic variation on microbiome differences within a controlled environment. Understanding the relationship between host-genetic and microbial variation also has biomedical implications, such as understanding why some humans are more susceptible to chronic inflammatory disorders like Crohns Disease and Ulcerative Colitis. To directly assess the relationship between host-genetic variation and microbiome variation, we performed a common garden experiment using laboratory lines of genetically divergent populations of threespine stickleback fish - a species that is an outbred model organism commonly used for determining the genetic basis of complex traits in the context of natural genetic variation. Using germ-free derivation and the powerful common garden design with these divergent lines, as well as hybrids between them, we detected clear associations between stickleback genetic dissimilarity and microbiome dissimilarity. Using genome-wide RAD-seq data we also identified regions of the genome underlying differences in microbiome composition. Importantly, we highlight that heritable morphological traits such as body size that are correlated with microbiome dissimilarity also need consideration in future microbiome studies.

evolutionary biology↗

bioRxiv2022

Novel mitochondrial genome rearrangements including duplications and extensive heteroplasmy in Antarctic Notothenioid Fishes

Mitochondrial genomes are known for their compact size and conserved gene order, however, recent studies employing long-read sequencing technologies have revealed the presence of atypical mitogenomes in some species. In this study, we assembled and annotated the mitogenomes of five Antarctic notothenioids, including four icefishes (Champsocephalus gunnari, C. esox, Chaenocephalus aceratus, and Pseudochaenuchthys georgianus) and the cold-specialized Trematomus borchgrevinki. Antarctic notothenioids are known to harbor some rearrangements in their mt genomes, however the extensive duplications in icefishes observed in our study have never been reported before. In the icefishes, we observed duplications of the protein coding gene ND6, two transfer RNAs, and the control region with different copy number variants present within the same individuals and with some ND6 duplications appearing to follow the canonical Duplication-Degeneration-Complementation (DDC) model in C. esox and C. gunnari. In addition, using long-read sequencing and k-mer analysis, we were able to detect extensive heteroplasmy in C. aceratus and C. esox. We also observed a large inversion in the mitogenome of T. borchgrevinki, along with the presence of tandem repeats in its control region. This study is the first in using long-read sequencing to assemble and identify structural variants and heteroplasmy in notothenioid mitogenomes and signifies the importance of long-reads in resolving complex mitochondrial architectures. Identification of such wide-ranging structural variants in the mitogenomes of these fishes could provide insight into the genetic basis of the atypical icefish mitochondrial physiology and more generally may provide insights about their potential role in cold adaptation.

evolutionary biology↗

bioRxiv2021

Leafy and Weedy Seadragon Genomes Connect Genic and Repetitive DNA Features to the Extravagant Biology of Syngnathid Fishes

Seadragons are a remarkable lineage of teleost fishes, and they are members of the family Syngnathidae renowned for having evolved male pregnancy. Comprising three known species, seadragons are widely recognized and admired for their fantastical body forms and coloration, and their specific habitat requirements have made them flagship representatives for marine conservation and natural history interests. Until recently, a gap has been the lack of significant genomic resources for seadragons. We have produced gene-annotated, chromosome-scale genome models for the leafy and weedy seadragon to advance investigations into evolutionary innovation and elaboration of morphological traits in seadragons as well as their pipefish and seahorse relatives. We identified several interesting features specific to seadragon genomes, including divergent non-coding regions near a developmental gene important for integumentary outgrowth, a high genome-wide density of repetitive DNA, and recent expansions of transposable elements and a vesicular trafficking gene family. Surprisingly, comparative analyses leveraging the seadragon genomes and additional syngnathid and outgroup genomes revealed striking, syngnathid-specific losses in the family of fibroblast growth factors (FGFs), which likely involve re-organization of highly conserved gene regulatory networks in ways that have not previously been documented in natural populations. The resources presented here serve as important tools for future evolutionary studies of developmental processes in syngnathids and will be a key resource for conservation studies of the extravagant seadragons and their relatives.

genomics↗

bioRxiv2019

QTL mapping of intestinal neutrophil variation and inflammation between threespine stickleback populations reveals links to neurodegenerative disease

Host selection is often required to foster beneficial microbial symbionts and suppress deleterious pathogens. In animals, the host immune system is at the center of this relationship. Failed host immune system-microbial interactions can result in a persistent inflammatory response in which the immune system indiscriminately attacks resident microbes, and at times the host cells themselves, leading to diseases such as Ulcerative Colitis, Crohns Disease, and Psoriasis. Host genetic variation has been linked to both microbiome diversity and to severity of such inflammatory disease states in humans. However, the microbiome and inflammatory states manifest as quantitative traits, which encompass many genes interacting with one another and the environment. The mechanistic relationships among all of these interacting components are still not clear. Developing natural genetic models of host-microbe interactions is therefore fundamental to understanding the complex genetics of these and other diseases. Threespine stickleback (Gasterosteus aculeatus) fish are a tractable model for attacking this problem because of abundant population-level genetic and phenotypic variation in the gut inflammatory response. Previous work in our laboratory identified genetically divergent stickleback populations exhibiting differences in intestinal neutrophil activity. We took advantage of this diversity to genetically map variation in an emblematic element of gut inflammation - intestinal neutrophil recruitment - using an F2-intercross mapping framework. We identified three regions of the genome associated with increased intestinal inflammation containing several promising candidate genes. Within these regions we found candidates in the Coagulation/Complement System, NFkB and MAPK pathways along with several genes associated with neurodegenerative diseases commonly accompanying intestinal inflammation as a secondary symptom. These findings highlight the utility of using naturally genetically diverse evolutionary mutant models such as threespine stickleback to better understand interactions among host genetic diversity and microbiome variation in health and disease states.

genetics↗

bioRxiv2018

Highly reproducible 16S sequencing facilitates measurement of host genetic influences on the stickleback gut microbiome

Multicellular organisms interact with resident microbes in important ways, and a better understanding of host-microbe interactions is aided by tools such as high-throughput 16S sequencing. However, rigorous evaluation of the veracity of these tools in a different context from which they were developed has often lagged behind. Our goal was to perform one such critical test by examining how variation in tissue preparation and DNA isolation could affect inferences about gut microbiome variation between two genetically divergent lines of threespine stickleback fish maintained in the same lab environment. Using careful experimental design and intensive sampling of individuals, we addressed technical and biological sources of variation in 16S-based estimates of microbial diversity. After employing a two-tiered bead beating approach consisting of tissue homogenization followed by microbial lysis in subsamples, we found an extremely minor effect of DNA isolation protocol relative to among-host microbial diversity differences. Individual abundance estimates for rare OTUs, however, showed much lower reproducibility. We found that the stickleback gut microbiome was highly variable, even among siblings housed together, but that an effect of host genotype (stickleback lineage) was detectable for some microbial taxa. Our findings demonstrate the importance of appropriately quantifying biological and technical variance components when attempting to understand major influences on high-throughput microbiome data.

microbiology↗