Biology subjects

Sterken, M.

Publications and source records attributed to Sterken, M..

4 recordsLinked to original sources

bioRxiv2020

Balancing selection maintains ancient genetic diversity in C. elegans

Across diverse taxa, selfing species have evolved independently from outcrossing species thousands of times. The transition from outcrossing to selfing significantly decreases the effective population size, effective recombination rate, and heterozygosity within a species. These changes lead to a reduction in genetic diversity, and therefore adaptive potential, by intensifying the effects of random genetic drift and linked selection. Within the nematode genus Caenorhabditis, selfing has evolved at least three times and all three species, including in the model organism Caenorhabditis elegans, show substantially reduced genetic diversity relative to outcrossing species. Selfing and outcrossing Caenorhabditis species are often found in the same niches, but we still do not know how selfing species with limited genetic diversity can adapt to these environments. Here, we examine the whole-genome sequences from 609 wild C. elegans strains isolated worldwide and show that genetic variation is concentrated in punctuated hyper-divergent regions that cover 20% of the C. elegans reference genome. These regions are enriched in environmental response genes that mediate sensory perception, pathogen response, and xenobiotic stress response. Population genomic evidence suggests that genetic diversity in these regions has been maintained by long-term balancing selection. Using long-read genome assemblies for 15 wild strains, we show that hyper-divergent haplotypes contain unique sets of genes and show levels of divergence comparable to levels found between Caenorhabditis species that diverged millions of years ago. These results provide an example for how species can avoid the evolutionary "dead end" associated with selfing.

evolutionary biology↗

bioRxiv2019

SIZ1 is a nuclear host target of the nematode effector GpRbp1 from Globodera pallida that acts as a negative regulator of basal plant defense to cyst nematodes

Soil-borne cyst nematodes are obligatory sedentary parasites that cause severe losses to cultivation of major crops such as potato and soybean. Cyst nematodes establish specialised permanent feeding sites within the roots of their host by manipulating plant morphology and physiology through secreted effectors. Here we identified host targets of effector GpRbp-1 and studied their roles in plant-nematode interactions. GpRbp-1 was found to interact in yeast and in planta with the potato and Arabidopsis homologues of Siz/PIAS-type E3 SUMO ligase SIZ1. Our results show that a pathogen effector targets the master regulator SIZ1 in plant cells, which has not been demonstrated earlier to our knowledge. The interaction of GpRbp-1 and SIZ1 localizes to the plant nucleus, suggesting that the nuclear functions of SIZ1 as regulator of plant immunity and physiology may be modulated by GpRbp-1. Furthermore, nematode infection assays and transcriptomic profiling indicate that SIZ1 is required for susceptibility to cyst nematodes. So, these data indicate that E3 SUMO ligases may play an important role in plant-nematode interactions. Based on the prediction of SUMO acceptor and interaction sites in GpRbp-1, a model is proposed in which the effector may recruit SIZ1 to be SUMOylated for full functionality in host cells.\n\nSignificance statementHere we show that a pathogen effector can target SIZ1, a key protein involved in regulating several aspects of plant biology, most likely to manipulate the SUMOylation of host proteins for successful infection of plants.

plant biology↗

bioRxiv2017

Natural genetic variation in C. elegans reveals genomic loci controlling metabolite levels

Metabolic homeostasis is sustained by complex biological networks responding to nutrient availability. Disruption of this equilibrium involving intricate interactions between genetic and environmental factors can lead to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we applied a quantitative genetic strategy using a Caenorhabditis elegans population consisting of 199 recombinant inbred lines (RILs) originally derived from crossing parental strains Bristol N2 and Hawaii CB4856. We focused on the genetic factors that control metabolite levels and measured fatty acid (FA) and amino acid (AA) composition in the 199 RILs using targeted metabolomics. For both FA and AA profiles, we observed large variation in metabolite levels with 32-82% heritability between the RILs. We performed metabolite-metabolite correlation analysis and detected strongly co-correlated metabolite clusters. To identify natural genetic variants responsible for the observed metabolite variations, we performed QTL mapping and detected 36 significant metabolite QTL (mQTL). We focused on the mQTL that displayed high significant linkage and heritability, including an mQTL for the FA C14:1 on chromosome I, and another mQTL for the FA C18:2 on chromosome IV. Using introgression lines (ILs) we were able to narrow down both mQTL to a 1.4 Mbp and a 3.6 Mbp region, respectively. Overall, this systems approach provides us with a powerful platform to study the genetic basis of C. elegans metabolism. It also allows us to investigate additional interventions, such as nutrients and stresses that maintain or disturb the regulatory network controlling metabolic homeostasis, and identify gene-by-environment interactions.

genomics↗

bioRxiv2017

Contribution Of Trans Regulatory eQTL To Cryptic Genetic Variation In C. elegans

BackgroundCryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce. Here we investigated the transcriptional architecture of CGV in response to rapid temperature changes in the nematode Caenorhabditis elegans. We analyzed regulatory variation in gene expression (and mapped eQTL) across the course of a heat stress and recovery response in a recombinant inbred population.\n\nResultsWe measured gene expression over three temperature treatments: i) control, ii) heat stress, and iii) recovery from heat stress. Compared to control, exposure to heat stress affected the transcription of 3305 genes, whereas 942 were affected in recovering worms. These affected genes were mainly involved in metabolism and reproduction. The gene expression pattern in recovering worms resembled both the control and the heat stress treatment. We mapped eQTL using the genetic variation of the recombinant inbred population and detected 2626 genes with an eQTL in the heat stress treatment, 1797 in the control, and 1880 in the recovery. The cis-eQTL were highly conserved across treatments. A considerable fraction of the trans-eQTL (40-57%) mapped to 19 treatment specific trans-bands. In contrast to cis-eQTL, trans-eQTL were highly environment specific and thus cryptic. Approximately 67% of the trans-eQTL were only induced in a single treatment, with heat-stress showing the most unique trans-eQTL.\n\nConclusionsThese results illustrate the highly dynamic pattern of CGV across three different environmental conditions that can be evoked by a stress response over a relatively short time-span (2 hours) and that CGV is mainly determined by response related trans regulatory eQTL.

genetics↗