Biology subjects

Riksen, J. A. G.

Publications and source records attributed to Riksen, J. A. G..

9 recordsLinked to original sources

bioRxiv2023

Disease-decreasing diversity: evidence for lowered parasite prevalence in microscopic nematode communities with higher species numbers

Biodiversity can affect parasite prevalence, a phenomenon widely studied in macroscopic organisms. However, data from microscopic communities is lacking, despite their essential role in ecosystem functioning and the unique experimental opportunities microscopic organisms offer. Here, we study diversity-disease effects in wild nematode communities by profiting from the molecular tools available in the well-studied model nematode Caenorhabditis elegans. Nanopore sequencing was used to characterize nematode community diversity and composition, whereas parasites were identified using nine distinct experimental assays based on fluorescent staining or fluorescent reporter strains. Our results indicate biotic stress is abundant in wild nematode communities. Moreover, in two assays, diversity-disease relations were observed: microsporidia and immune system activation were more often detected in relatively species-poor communities. Other assays, targeting different parasites, were without diversity-disease relations. Together, this study provides the first demonstration of diversity-disease effects in microbial communities and establishes the use of nematode communities as model systems for disease dilution.

ecology↗

bioRxiv2022

Two sides to every coin: complementary introgression line populations in Caenorhabditis elegans

Quantitative genetics seeks to understand the role of allelic variation in trait differences. Introgression lines (ILs) contain a single genetic locus introgressed into another genetic background, and are one of the most powerful quantitative trait locus (QTL) mapping designs. However, albeit useful for QTL discovery, this homogenous background confounds genetic interactions. Here, we created an IL population with N2 segments in a CB4856 background (ILCB4856), reciprocal to an N2 background with CB4856 introgressions population (ILN2). The ILCB4856 panel comprises a population of 145 strains with sequencing confirmed N2 introgressions in a CB4856 background. A core set of 87 strains covering the entire genome was selected. We present three experiments demonstrating the power of the reciprocal IL panels. First, we performed QTL mapping identifying new regions associated with lifespan. Second, the existence of opposite-effect loci regulating heat-stress survival is demonstrated. Third, by combining ILN2 and ILCB4856 strains, an interacting expression QTL was uncovered. In conclusion, the reciprocal IL panels are a unique and ready-to-use resource to identify, resolve, and refine complex trait architectures in C. elegans.

genetics↗

bioRxiv2021

The genetic architecture underlying body-size traits plasticity over different temperatures and developmental stages in Caenorhabditis elegans

Most ectotherms obey the temperature-size rule, meaning they grow larger in a colder environment. This raises the question of how the interplay between genes and temperature affect the body size of ectotherms. Despite the growing body of literature on the physiological life-history and molecular genetic mechanism underlying the temperature-size rule, the overall genetic architecture orchestrating this complex phenotype is not yet fully understood. One approach to identify genetic regulators of complex phenotypes is Quantitative Trait Locus (QTL) mapping. Here, we explore the genetic architecture of body size phenotypes, and plasticity of body-size phenotypes in different temperatures using Caenorhabditis elegans as a model ectotherm. We used 40 recombinant inbred lines (RILs) derived from N2 and CB4856, which were reared at four different temperatures (16{degrees}C, 20{degrees}C, 24{degrees}C, and 26{degrees}C) and measured at two developmental stages (L4 and adult). The animals were measured for body length, width at vulva, body volume, length/width ratio, and seven other body-size traits. The genetically diverse RILs varied in their body-size phenotypes with heritabilities ranging from 0.0 to 0.99. We detected 18 QTL underlying the body-size traits across all treatment combinations, with the majority clustering on Chromosome X. We hypothesize that the Chromosome X QTL could result from a known pleiotropic regulator - npr-1 - known to affect the body size of C. elegans through behavioral changes. We also found five plasticity QTL of body-size which three of them colocalized with some body-size QTL at certain temperature. In conclusion, our findings shed more light on multiple loci affecting body size plasticity and the possibility of co-regulation of traits and traits plasticity by the same loci under different environment.

genetics↗

bioRxiv2020

Punctuated loci on chromosome IV determine natural variation in Orsay virus susceptibility of Caenorhabditis elegans strains Bristol N2 and Hawaiian CB4856

Host-pathogen interactions play a major role in evolutionary selection and shape natural genetic variation. The genetically distinct Caenorhabditis elegans strains, Bristol N2 and Hawaiian CB4856, are differentially susceptible to the Orsay virus (OrV). Here we report the dissection of the genetic architecture of susceptibility to OrV infection. We compare OrV infection in the relatively resistant wild-type CB4856 strain to the more susceptible canonical N2 strain. To gain insight into the genetic architecture of viral susceptibility, 52 fully sequenced recombinant inbred lines (CB4856 x N2 RILs) were exposed to OrV. This led to the identification of two loci on chromosome IV associated with OrV resistance. To verify the two loci and gain additional insight into the genetic architecture controlling virus infection, introgression lines (ILs) that together cover chromosome IV, were exposed to OrV. Of the 27 ILs used, 17 had an CB4856 introgression in an N2 background and 10 had an N2 introgression in a CB4856 background. Infection of the ILs confirmed and fine-mapped the locus underlying variation in OrV susceptibility and we found that a single nucleotide polymorphism in cul-6 contributes to the difference in OrV susceptibility between N2 and CB4856. An allele swap experiment showed the strain CB4856 became more susceptible by having an N2 cul-6 allele, although having the CB4856 cul-6 allele did not increase resistance in N2. Additionally, we found that multiple strains with non-overlapping introgressions showed a distinct infection phenotype from the parental strain, indicating that there are punctuated locations on chromosome IV determining OrV susceptibility. Thus, our findings reveal the genetic complexity of OrV susceptibility in C. elegans and suggest that viral susceptibility is governed by multiple genes.

genetics↗

bioRxiv2019

Dissecting the eQTL micro-architecture in Caenorhabditis elegans

The study of expression quantitative trait loci (eQTL) using natural variation in inbred populations has yielded detailed information about the transcriptional regulation of complex traits. Studies on eQTL using recombinant inbred lines (RILs) led to insights on local and distant regulatory loci of transcript abundance. However, determining the underlying causal polymorphic genes or variants is difficult, but ultimately essential for the understanding of regulatory networks of complex traits. This requires insight into whether associated loci are single eQTL or a combination of closely linked eQTL, and how this QTL micro-architecture depends on the environment. We addressed these questions by mapping eQTL in N2 x CB4856 C. elegans RIL populations across three different environments (control, heat-stress, and recovery). To test for independent replication of the RIL eQTL, we used introgression lines (ILs). Both populations indicate that the overall heritability, number, and position of eQTL differed among environments. Across environments we were able to replicate 70% of the local- and 40% of the distant-eQTL using the ILs. Simulation models revealed that additive effects explain up to 60-93% of RIL/IL heritability across environments. Closely linked eQTL explained up to 40% of RIL/IL heritability in the control environment whereas only 7% in the heat-stress and recovery environments. In conclusion, we show that reproducibility of eQTL was higher for local vs. distant eQTL and that the environment affects the eQTL micro-architecture.

genetics↗

bioRxiv2019

Selection and gene flow shape niche-associated copy-number variation of pheromone receptor genes

From quorum sensing in bacteria to pheromone signaling in social insects, chemical communication mediates interactions among individuals in a local population. In Caenorhabditis elegans, ascaroside pheromones can dictate local population density, in which high levels of pheromones inhibit the reproductive maturation of individuals. Little is known about how natural genetic diversity affects the pheromone responses of individuals from diverse habitats. Here, we show that a niche-associated copy-number variation (CNV) of pheromone receptor genes contributes to natural differences in pheromone responses. We found putative loss-of-function deletions that reduce copy number of duplicated pheromone receptor genes (srg-36 and srg-37), which were shown previously to be selected in population-dense laboratory cultures. A common natural deletion in the less functional copy (srg-37) arose from a single ancestral population that spread throughout the world and underlies reduced pheromone sensitivity across the global C. elegans population. This deletion is enriched in wild strains that were isolated from a rotting fruit niche, where proliferating populations are often found. Taken together, these results demonstrate that selection and gene flow together shape the copy number of pheromone receptor genes in natural C. elegans populations to facilitate local adaptation to diverse niches.

evolutionary biology↗

bioRxiv2019

Balancing selection shapes the Intracellular Pathogen Response in natural Caenorhabditis elegans populations

Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation in the Intracellular Pathogen Response (IPR), an important antiviral pathway in the model organism Caenorhabditis elegans against Orsay virus (OrV). The IPR involves transcriptional activity of 80 genes including the pals-genes. We examine the genetic variation in the pals-family for traces of selection and explore the molecular and phenotypic effects of having distinct pals-gene alleles. Genetic analysis of 330 global C. elegans strains reveals that genetic diversity within the IPR-related pals-genes can be categorized in a few haplotypes worldwide. Importantly, two key IPR regulators, pals-22 and pals-25, are in a genomic region carrying signatures of balancing selection, suggesting that different evolutionary strategies exist in IPR regulation. We infected eleven C. elegans strains that represent three distinct pals-22 pals-25 haplotypes with Orsay virus to determine their susceptibility. For two of these strains, N2 and CB4856, the transcriptional response to infection was also measured. The results indicate that pals-22 pals-25 haplotype shapes the defense against OrV and host genetic variation can result in constitutive activation of IPR genes. Our work presents evidence for balancing genetic selection of immunity genes in C. elegans and provides a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.

genetics↗

bioRxiv2017

A Point Of No Return Leading To Death During Heat-Shock In C. elegans

There is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments. Here, we studied global gene expression profiles during 12 hours of heat stress in the nematode C. elegans. Using a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3-4 hours into the stress response, separating an initially highly dynamic phase from a later relatively stagnant phase. This turning point in expression dynamics coincided with a phenotypic turning point, as shown by a strong decrease in movement, survival and, progeny count in the days following the stress. Both detectable at transcriptional and phenotypic level, this study pin-points a relatively small time frame during heat stress at which enough damage is accumulated, making it impossible to recover the next few days.

genomics↗

bioRxiv2017

Genetical genomics reveals Ras/MAPK modifier loci

The oncogenic Ras/MAPK pathway is evolutionary conserved across metazoans and is essential for many cellular functions. Mutant screens in the model nematode Caenorhabditis elegans have been invaluable for elucidating Ras/MAPK pathway characteristics and identification of the genes involved. Almost all of these screens have been conducted in a single genetic background. However, phenotypic traits of induced mutations can vary widely depending on the genetic background. At the moment, we lack insight into how different genetic backgrounds modulate Ras/MAPK-signaling and which genetic modifiers are involved.\n\nWe previously introduced a gain-of-function mutation in the Ras/MAPK pathway gene let-60 in over 200 recombinant inbred lines (mutant introgressed RILs: miRILs) and detected genetic modifiers affecting this pathway by studying variation in vulval development. In the present study, we investigate how gene expression regulation is affected by the let-60 gain-of-function mutation and the genetic background by mapping eQTL using 33 miRILs. We found that the majority ([~]73%) of the 1516 detected cis-eQTL are not specific for the let-60 mutation, whereas most ([~]76%) of the 898 detected trans-eQTL are associated with the let-60 mutation. We detected 6 eQTL trans-bands that were specific for the interaction between the genetic background and the mutation. One of these eQTL hotspots co-localizes with the previously identified polymorphic Ras/MAPK modifier amx-2. Comparing gene expression profiles between transgenic lines expressing either the N2 or the CB4856 alleles of amx-2 showed the involvement of amx-2 in 79% of the trans-eQTLs for genes mapping to this trans-band.\n\nTogether, our results have revealed hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in C. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.

genetics↗