Biology subjects

Moser, K. A.

Publications and source records attributed to Moser, K. A..

7 recordsLinked to original sources

bioRxiv2026

Recombination and repetitive genomic landscapes are decoupled in a close relative of Caenorhabditis elegans

Genomes exhibit chromosomal heterogeneity. Distributions of genes, repetitive elements, and polymorphisms are not uniform along chromosomes in multiple species. One explanation for these patterns is recombination rate variation. As recombination interacts with selection to shape the evolutionary fates of alleles, recombination rate variation could promote differences in the chromosomal distribution of genomic features. Thus, clarifying the relationship between recombination rates and genomic organization is a major goal of genetics. In the nematode Caenorhabditis elegans, recombination rate correlates with multiple genomic features that are non-uniformly distributed along chromosomes; recombination rates and repeats are higher on chromosome ends compared to chromosome centers. Its closest known relative, C. inopinata, harbors a radically altered genome with nearly uniform chromosomal distributions of repetitive elements. Is this dramatic change in genomic organization connected to the evolution of recombination rates? Here, we describe a genetic map of C. inopinata constructed via whole-genome sequencing of 180 individual F2 recombinants. This reveals four chromosomes have a conserved recombination rate domain structure whereas two other chromosomes harbor divergent, more uniform recombination rate distributions. Comparisons of these intrachromosomal recombination rates with genomic features reveal little covariation between recombination rate, diversity, gene density, and repeat content in C. inopinata (in stark contrast to most Caenorhabditis species). This suggests that the evolution of recombination may not be entirely responsible for the atypical uniform distribution of repetitive elements across C. inopinata chromosomes. Taken together, these observations reveal that recombination rates can be decoupled from the genomic organization of repetitive elements.

genomics↗

bioRxiv2025

A novel, fig-associated microbe promotes reproductive success via variable life history mechanisms in C. elegans and C. inopinata

Variation in life history strategies is among the most striking features of animal diversity. Simultaneously, the microbes an animal interacts with are a critical and dynamic aspect of the host environment that can have profound impacts on their life history traits. As microbial environments diverge across animal lineages, life histories and their responses to such microbial contexts are expected to evolve as a consequence. Caenorhabditis nematodes are bacterivores that exhibit a diversity of life history strategies and fill diverse ecological niches. C. elegans thrives on rotting plants and grows rapidly with high fecundity; C. inopinata thrives in fresh figs and grows more slowly with lower fecundity. To understand how hosts with divergent life histories and ecologies respond to the microbes they interact with, we isolated over forty bacterial species from the natural fig environment of C. inopinata. This microbial survey revealed an isolate, Klebsiella sp. WOUb2, that doubles the population growth rate of C. inopinata. While this isolate also increases the population growth rate of C. elegans, Klebsiella sp. WOUb2 increases individual fecundity and developmental rate in C. elegans, whereas it only increases developmental rate of C. inopinata. Thus, fitness is modulated by variable life history mechanisms in the two species. Comparisons with nucleotide databases reveal Klebsiella sp. WOUb2 is closely related to other Klebsiella isolates known to influence Caenorhabditis nematode fitness. Additionally, the similarity of Klebsiella sp. WOUb2 to microbes associated with fig wasps and figs suggests C. inopinata frequently encounters this microbe in its natural context. Taken together, this shows that different physiological responses can underlie conserved, beneficial interspecific interactions.

evolutionary biology↗

bioRxiv2024

The Bacteria of a Fig Microcommunity

Understanding the biotic drivers of diversity is a major goal of microbial ecology. One approach towards tackling this issue is to interrogate relatively simple communities that are easy to observe and perturb. Figs (syconia) of the genus Ficus represent such a system. Here, we describe the microbial communities of Ficus septica figs, which are associated with the nematode Caenorhabditis inopinata (the sister species of the C. elegans genetic model system). In 2019, 38 Ficus septica figs (across 12 plants in Taiwan) were dissected, and metadata such as foundress wasp number and nematode occupancy were collected for each fig. Suspensions derived from interior fig material and fig surface washes were prepared for 16S microbial metabarcoding. Over 3,000 OTUs were detected, and microbial communities were dominated by members of Proteobacteria, Bacteroidota, and Actinobacteriota. Although microbial communities of fig exteriors and interiors can be distinguished, levels of microbial alpha diversity were comparable across these areas of the fig. Nematodes likewise had no detectable impact on microbial alpha diversity, although nematodes were associated with a modest change in microbial community composition. A handful of OTUs (associated with the genera Kosokonia, Ochobactrum, and Stenotrophomonas) revealed potential differential abundance among figs varying in nematode occupancy. Additionally, foundress wasp number was negatively correlated with microbial alpha diversity. These findings set the stage for future studies that directly test the role of nematode and wasp occupancy on microbial communities, as well as investigations that probe nematode-microbe interactions through laboratory experiments. Taken together, these results constitute a fundamental step in characterizing the natural microbial communities of figs and Caenorhabditis nematodes. ImportanceUnraveling why different species live in different places is a longstanding open question in ecology, and it is clear that interspecific interactions among species are a major contributor to species distributions. Ficus figs are a useful system for ecological studies because they are relatively simple microcosms where characterizing animal community composition of multiple samples is straightforward. Additionally, Caenorhabditis inopinata, a close relative of the C. elegans genetic model system, thrives in Ficus septica figs. Here, we tie 16S microbial metabarcoding to nematode and wasp occupancy data to understand the causes of bacterial community composition in F. septica figs. We found that microbial composition, but not total diversity, varies among fig surface and interiors. Likewise, we found that nematode occupancy impacts microbial composition but not alpha diversity. Moreover, we show that as the number of foundress wasps increases, the microbial alpha diversity decreases. Finally, we identified OTUs that are potentially associated with nematode occupancy. Taken together, these results represent a key step in describing a microcommunity wherein ecological genetic hypotheses can be tested, as well as one that can potentially reveal the roles of uncharacterized genes in established model systems.

ecology↗

bioRxiv2023

Differentiation of hypervirulent and classical Klebsiella pneumoniae with acquired drug resistance

Distinguishing hypervirulent (hvKp) from classical Klebsiella pneumoniae (cKp) strains is important for clinical care, surveillance, and research. Some combination of iucA, iroB, peg-344, rmpA, and rmpA2 are most commonly used, but it is unclear what combination of genotypic or phenotypic markers (e.g. siderophore concentration, mucoviscosity) most accurately predicts the hypervirulent phenotype. Further, acquisition of antimicrobial resistance may affect virulence and confound identification. Therefore, 49 K. pneumoniae strains that possessed some combination of iucA, iroB, peg-344, rmpA, and rmpA2 and had acquired resistance were assembled and categorized as hypervirulent hvKp (hvKp) (N=16) or cKp (N=33) via a murine infection model. Biomarker number, siderophore production, mucoviscosity, virulence plasmids Mash/Jaccard distances to the canonical pLVPK, and Kleborate virulence score were measured and evaluated to accurately differentiate these pathotypes. Both stepwise logistic regression and a CART model were used to determine which variable was most predictive of the strain cohorts. The biomarker count alone was the strongest predictor for both analyses. For logistic regression the area under the curve for biomarker count was 0.962 (P = 0.004). The CART model generated the classification rule that a biomarker count = 5 would classify the strain as hvKP, resulting in a sensitivity for predicting hvKP of 94% (15/16), a specificity of 94% (31/33), and an overall accuracy of 94% (46/49). Although a count of [≥] 4 was 100% (16/16) sensitive for predicting hvKP, the specificity and accuracy decreased to 76% (25/33) and 84% (41/49) respectively. These findings can be used to inform the identification of hvKp. ImportanceHypervirulent Klebsiella pneumoniae (hvKp) is a concerning pathogen that can cause life-threatening infections in otherwise healthy individuals. Importantly, although strains of hvKp have been acquiring antimicrobial resistance, the effect on virulence is unclear. Therefore, it is of critical importance to determine whether a given antimicrobial resistant K. pneumoniae isolate is hypervirulent. This report determined which combination of genotypic and phenotypic markers could most accurately identify hvKp strains with acquired resistance. Both logistic regression and a machine-learning prediction model demonstrated that biomarker count alone was the strongest predictor. The presence of all 5 of the biomarkers iucA, iroB, peg-344, rmpA, and rmpA2 was most accurate (94%); the presence of [≥] 4 of these biomarkers was most sensitive (100%). Accurately identifying hvKp is vital for surveillance and research, and the availability of biomarker data could alert the clinician that hvKp is a consideration, which in turn would assist in optimizing patient care.

microbiology↗

bioRxiv2022

Finding mutations in all the wrong places: Prevalence of knock-down resistance F1534S 1 mutations among Aedes albopictus (family: Culicidae, order: Diptera) in North Carolina

BackgroundKnock-down resistance (kdr) mutations in the voltage gated sodium channel gene of Aedes species mosquitoes are biomarkers for resistance to pyrethroid insecticides. In the United States, few studies have reported kdr mutations among Aedes albopictus (family: Culicidae, order: Diptera, Skuse, 1895) populations. In this study we sought to explore the potential for permethrin-impregnated uniforms worn by military servicemembers to drive kdr emergence. Methods and ResultsWe collected 538 Aedes albopictus mosquitoes, including 156 from 4 sites at Fort Bragg (exposed), North Carolina and 382 from 15 sites in Wake County (control), North Carolina to compare the prevalence of kdr mutations. Of those successfully sequenced, we identified 12 (3.0%) mosquitoes with kdr mutations, all of which were attributed to variants at position 1534 within domain 3. All mutations were found in mosquitoes collected at Wake County sites; no mutations were identified at Fort Bragg. There was a focus of mutations observed at the Wake County sites with approximately 92% (11 of 12) of the mosquitoes with the mutation coming from one site, where kdr mutations represented 24.4% (11 of 45) of all mosquitoes collected. ConclusionsOur study did not show any evidence that universal implementation of permethrin-impregnated uniforms drives the development of resistance. In contrast, we observed highly focal resistance in a suburban area of Raleigh, which may be attributable to peri-domestic mosquito control activities that involve area dispersal of pyrethroid insecticides. More robust surveillance is needed to monitor the emergence and spread of resistance. AUTHOR SUMMARYResistance to commonly employed insecticides among Aedes albopictus (family: Culicidae, order: Diptera, Skuse, 1895) mosquitoes poses as a substantial public health threat. In this study we sought to explore the potential for permethrin-impregnated uniforms worn by military servicemembers to drive emergence of resistance to pyrethroid insecticides by collecting and testing mosquitoes from both military and civilian sites. Overall, we did not identify mosquitoes harboring resistance at Ft. Bragg, but did find a focus of resistance in sub-urban Raleigh, which may be driven by commercial, peri-domestic mosquito control activities. These results suggest that resistance to pyrethroid insecticides may be more prevalent in the United States than previously known, but highly heterogenous. More robust surveillance is needed to monitor the emergence and spread of resistance.

ecology↗

bioRxiv2020

Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes

High-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programs, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high-burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania country-wide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome-wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, roughly separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from geographically close districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts, and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region-level complexity-of-infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared. SIGNIFICANCEDocumenting dynamics of malaria parasite genomics in high-transmission settings at scale in sub-Saharan Africa is critical for policy and decision making to support ongoing malaria elimination initiatives. Using molecular inversion probes, we genotyped over 1,000 Tanzanian Plasmodium falciparum samples collected country-wide in 2017 at hundreds of variable polymorphic positions across the genome. Frequencies of known drug resistance mutations were higher in northern districts of the country compared to the south. Results also showed a distinct isolation-by-distance pattern (whereby increasing geographic distance was correlated with decreasing genetic relatedness), as well as signals of higher genetic sharing between several southern districts. These results provide, for the first time, a picture of current within-country diversity of Tanzanian P. falciparum populations.

genomics↗

bioRxiv2019

Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential

BackgroundPlasmodium falciparum (Pf) whole-organism sporozoite vaccines have provided excellent protection against controlled human malaria infection (CHMI) and naturally transmitted heterogeneous Pf in the field. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy (VE) have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions.\n\nMethodsWhole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequence polymorphisms and structural variants in each strain relative to the reference Pf 3D7 (a clone of NF54) genome. Strains were compared to each other and to clinical isolates from South America, Sub-Saharan Africa, and Southeast Asia.\n\nResultsWhile few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains both genome-wide and within regulatory and immunologically important regions, including in pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contribute to diversity in immunologically important regions of the genomes as detected through in silico CD8+ T cell epitope predictions. Of all heterologous strains, NF135.C10 consistently had the highest number of unique predicted epitope sequences when compared to NF54, while NF166.C8 had the lowest. Comparison to global clinical isolates revealed that these four strains are representative of their geographic region of origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently-formed drug resistant subpopulations present in the Greater Mekong Sub-region.\n\nConclusionsThese results are assisting the interpretation of VE of whole-organism vaccines against homologous and heterologous CHMI, and may be useful in informing the choice of strains for inclusion in region-specific or multi-strain vaccines.

genomics↗