J. Riksen - Academia.edu (original) (raw)
Papers by J. Riksen
G3 (Bethesda, Md.), 2012
The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of m... more The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in an N2 × CB4856 recombinant inbred population of the nematode Caenorhabditis elegans. In particular, we showed that the number of eQTL decreased with age. Here, we investigated the reason for this decrease by combining gene expression profiles at three ages in the wild types N2 and CB4856 with the reported expression profiles of the RIL population. We determined heritability and transgression (when gene expression levels in the RILs are more extreme than the parents) and investigated their relation with eQTL changes with age. Transgressive segregation was widespread but depended on physiological age. The percentage of genes with an eQTL increased with a higher heritability in young worms. However, for old worms this percentage hardly increased. Using ...
C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling component... more C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical Wnt-pathway. Together with Wnt effector pop-1, bar-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.
The Open Natural Products Journal, 2009
Nematicidal activity of extracts from plants was assayed against Meloidogyne incognita. In labora... more Nematicidal activity of extracts from plants was assayed against Meloidogyne incognita. In laboratory assays extracts from tobacco (Nicotiana tabacum L), clove (Syzygium aromaticum L), betelvine (Piper betle L), and sweet flag (Acorus calamus L) were most effective in killing the nematode, with an EC 50 that was 5-10 times lower than the EC 50 of the synthetic pesticides chlorpyrifos, carbosulfan and deltamethrin. The shapes of the dead nematodes differed in a characteristic way, and groups of pesticides and plant extracts could clearly be distinguished based on this phenomenon, which may be an indicator for the modes of action of the tested pesticides. In a greenhouse bioassay clove bud and betelvine were tested as mulch. Experiments revealed that the total number of live nematodes on roots of pepper plants treated with mulch of the clove bud was 7% of that of the controls and did not differ significantly from that of plants treated with the recommended synthetic pesticide carbofuran. The application of clove buds as a botanical pesticide for future use against nematodes is highly promising since clove is the 6 th major plant grown on Bangka Island, and the market value of clove has decreased sharply over the last years.
International Journal of Health Planning and Management - INT J HEALTH PLAN MANAGE, 2004
Nucleic Acids Research, 2009
Caenorhabditis elegans wild-type N2 and CB4856 are increasingly being used for mapping genes unde... more Caenorhabditis elegans wild-type N2 and CB4856 are increasingly being used for mapping genes underlying complex traits. To speed up mapping and gene discovery, introgression lines (ILs) offer a powerful tool for more efficient QTL identification. We constructed a library of 90 ILs, each carrying a single homozygous CB4856 genomic segment introgressed into the genetic background of N2. The ILs were genotyped by 123 single-nucleotide polymorphism (SNP) markers. The proportion of the CB4856 segments in most lines does not exceed 3%, and together the introgressions cover 96% of the CB4856 genome. The value of the IL library was demonstrated by identifying novel loci underlying natural variation in two ageing-related traits, i.e. lifespan and pharyngeal pumping rate. Bin mapping of lifespan resulted in six QTLs, which all have a lifespan-shortening effect on the CB4856 allele. We found five QTLs for the decrease in pumping rate, of which four colocated with QTLs found for average lifespan. This suggests pleiotropic or closely linked QTL associated with lifespan and pumping rate. Overall, the presented IL library provides a versatile resource toward easier and efficient fine mapping and functional analyses of loci and genes underlying complex traits in C. elegans.
Heredity, 2007
Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the e... more Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the evolution of life histories. Knowledge of the molecular genetic basis of plasticity and GEI provides insight into the underlying mechanisms of life-history changes in different environments. We used a genomewide single-nucleotide polymorphism map in a recombinant N2 x CB4856 inbred panel of the nematode Caenorhabditis elegans to study the genetic control of phenotypic plasticity to temperature in four fitness-related traits, that is, age at maturity, fertility, egg size and growth rate. We mapped quantitative trait loci (QTL) for the respective traits at 12 and 24 degrees C, as well as their plasticities. We found genetic variation and GEI for age at maturity, fertility, egg size and growth rate. GEI in fertility and egg size was attributed to changes in rank order of reaction norms. In case of age at maturity and growth rate, GEI was caused mainly by differences in the among-line variance. In total, 11 QTLs were detected, five QTL at 12 degrees C and six QTL at 24 degrees C, which were associated with life-history traits. Five QTL associated with age at maturity, fertility and growth rate showed QTL x environment interaction. These colocalized with plasticity QTL for the respective traits suggesting allelic sensitivity to temperature. Further fine mapping, complementation analyses and gene silencing are planned to identify candidate genes underlying phenotypic plasticity for age at maturity, fertility and growth.
Heredity, 2007
Empirical evidence is mounting to suggesting that genetic correlations between life-history trait... more Empirical evidence is mounting to suggesting that genetic correlations between life-history traits are environment specific. However, detailed knowledge about the loci underlying genetic correlations in different environments is scant. Here, we studied the influence of temperature (121C and 241C) on the genetic correlations between egg size, egg number and body mass in the nematode Caenorhabditis elegans. We used a quantitative trait loci (QTL) approach based on a genetic map with evenly spaced single nucleotide polymorphism markers in an N2 Â CB4856 recombinant inbred panel. Significant genetic correlations between various traits were found at both temperatures. We detected pleiotropic or closely linked QTL, which supported the negative correlation between egg size and egg number at 121C, the positive correlation across temperatures for body mass, and the positive correlation between body mass and egg size at 121C. The results indicate that specific loci control the covariation in these life-history traits and the locus control is prone to environmental conditions.
Genetics, 2010
Alternative splicing is considered a major mechanism for creating multicellular diversity from a ... more Alternative splicing is considered a major mechanism for creating multicellular diversity from a limited repertoire of genes. Here, we performed the first study of genetic variation controlling alternative splicing patterns by comprehensively identifying quantitative trait loci affecting the differential expression of transcript isoforms in a large recombinant inbred population of Caenorhabditis elegans, using a new generation of whole-genome very-high-density oligonucleotide microarrays. Using 60 experimental lines, we were able to detect 435 genes with substantial heritable variation, of which 36% were regulated at a distance (in trans). Nonetheless, we find only a very small number of examples of heritable variation in alternative splicing (22 transcripts), and most of these genes colocalize with the associated genomic loci. Our findings suggest that the regulatory mechanism of alternative splicing in C. elegans is robust toward genetic variation at the genome-wide scale, which is in striking contrast to earlier observations in humans.
Ecological Applications, 2007
This study aims to reveal whether complexity, namely, community and trophic structure, of chronic... more This study aims to reveal whether complexity, namely, community and trophic structure, of chronically stressed soil systems is at increased risk or remains stable when confronted with a subsequent disturbance. Therefore, we focused on a grassland with a history of four centuries of patchy contamination. Nematodes were used as model organisms because they are an abundant and trophically diverse group and representative of the soil food web and ecosystem complexity. In a field survey, a relationship between contaminants and community structures was established. Following, two groups of soil mesocosms from the field that differed in contamination level were exposed to different disturbance regimes, namely, to the contaminant zinc and a heat shock. The zinc treatment revealed that community structure is stable, irrespective of soil contamination levels. This implies that centuries of exposure to contamination led to adaptation of the soil nematode community irrespective of the patchy distribution of contaminants. In contrast, the heat shock had adverse effects on species richness in the highly contaminated soils only. The total nematode biomass was lower in the highly contaminated field samples; however, the biomass was not affected by zinc and heat treatments of the mesocosms. This means that density compensation occurred rapidly, i.e., tolerant species quickly replaced sensitive species. Our results support the hypothesis that the history of contamination and the type of disturbance determine the response of communities. Despite that ecosystems may be exposed for centuries to contamination and communities show adaptation, biodiversity in highly contaminated sites is at increased risk when exposed to a different disturbance regime. We discuss how the loss of higher trophic levels from the entire system, such as represented by carnivorous nematodes after the heat shock, accompanied by local biodiversity loss at highly contaminated sites, may result in detrimental effects on ecosystem functions.
Organismal development is the most dynamic period of the life cycle, yet we have only a rough und... more Organismal development is the most dynamic period of the life cycle, yet we have only a rough understanding of the dynamics of gene expression during adolescent transition. Here we show that adolescence in Caenorhabditis elegans is characterized by a spectacular expression shift of conserved and highly polymorphic genes. Using a high resolution time series we found that in adolescent worms over 10,000 genes changed their expression. These genes were clustered according to their expression patterns. One cluster involved in chromatin remodelling showed a brief up-regulation around 50 h post-hatch. At the same time a spectacular shift in expression was observed. Sequence comparisons for this cluster across many genotypes revealed diversifying selection. Strongly up-regulated genes showed signs of purifying selection in non-coding regions, indicating that adolescence-active genes are constrained on their regulatory properties. Our findings improve our understanding of adolescent transition and help to eliminate experimental artefacts due to incorrect developmental timing.
G3 (Bethesda, Md.), 2012
The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of m... more The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in an N2 × CB4856 recombinant inbred population of the nematode Caenorhabditis elegans. In particular, we showed that the number of eQTL decreased with age. Here, we investigated the reason for this decrease by combining gene expression profiles at three ages in the wild types N2 and CB4856 with the reported expression profiles of the RIL population. We determined heritability and transgression (when gene expression levels in the RILs are more extreme than the parents) and investigated their relation with eQTL changes with age. Transgressive segregation was widespread but depended on physiological age. The percentage of genes with an eQTL increased with a higher heritability in young worms. However, for old worms this percentage hardly increased. Using ...
C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling component... more C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical Wnt-pathway. Together with Wnt effector pop-1, bar-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.
The Open Natural Products Journal, 2009
Nematicidal activity of extracts from plants was assayed against Meloidogyne incognita. In labora... more Nematicidal activity of extracts from plants was assayed against Meloidogyne incognita. In laboratory assays extracts from tobacco (Nicotiana tabacum L), clove (Syzygium aromaticum L), betelvine (Piper betle L), and sweet flag (Acorus calamus L) were most effective in killing the nematode, with an EC 50 that was 5-10 times lower than the EC 50 of the synthetic pesticides chlorpyrifos, carbosulfan and deltamethrin. The shapes of the dead nematodes differed in a characteristic way, and groups of pesticides and plant extracts could clearly be distinguished based on this phenomenon, which may be an indicator for the modes of action of the tested pesticides. In a greenhouse bioassay clove bud and betelvine were tested as mulch. Experiments revealed that the total number of live nematodes on roots of pepper plants treated with mulch of the clove bud was 7% of that of the controls and did not differ significantly from that of plants treated with the recommended synthetic pesticide carbofuran. The application of clove buds as a botanical pesticide for future use against nematodes is highly promising since clove is the 6 th major plant grown on Bangka Island, and the market value of clove has decreased sharply over the last years.
International Journal of Health Planning and Management - INT J HEALTH PLAN MANAGE, 2004
Nucleic Acids Research, 2009
Caenorhabditis elegans wild-type N2 and CB4856 are increasingly being used for mapping genes unde... more Caenorhabditis elegans wild-type N2 and CB4856 are increasingly being used for mapping genes underlying complex traits. To speed up mapping and gene discovery, introgression lines (ILs) offer a powerful tool for more efficient QTL identification. We constructed a library of 90 ILs, each carrying a single homozygous CB4856 genomic segment introgressed into the genetic background of N2. The ILs were genotyped by 123 single-nucleotide polymorphism (SNP) markers. The proportion of the CB4856 segments in most lines does not exceed 3%, and together the introgressions cover 96% of the CB4856 genome. The value of the IL library was demonstrated by identifying novel loci underlying natural variation in two ageing-related traits, i.e. lifespan and pharyngeal pumping rate. Bin mapping of lifespan resulted in six QTLs, which all have a lifespan-shortening effect on the CB4856 allele. We found five QTLs for the decrease in pumping rate, of which four colocated with QTLs found for average lifespan. This suggests pleiotropic or closely linked QTL associated with lifespan and pumping rate. Overall, the presented IL library provides a versatile resource toward easier and efficient fine mapping and functional analyses of loci and genes underlying complex traits in C. elegans.
Heredity, 2007
Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the e... more Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the evolution of life histories. Knowledge of the molecular genetic basis of plasticity and GEI provides insight into the underlying mechanisms of life-history changes in different environments. We used a genomewide single-nucleotide polymorphism map in a recombinant N2 x CB4856 inbred panel of the nematode Caenorhabditis elegans to study the genetic control of phenotypic plasticity to temperature in four fitness-related traits, that is, age at maturity, fertility, egg size and growth rate. We mapped quantitative trait loci (QTL) for the respective traits at 12 and 24 degrees C, as well as their plasticities. We found genetic variation and GEI for age at maturity, fertility, egg size and growth rate. GEI in fertility and egg size was attributed to changes in rank order of reaction norms. In case of age at maturity and growth rate, GEI was caused mainly by differences in the among-line variance. In total, 11 QTLs were detected, five QTL at 12 degrees C and six QTL at 24 degrees C, which were associated with life-history traits. Five QTL associated with age at maturity, fertility and growth rate showed QTL x environment interaction. These colocalized with plasticity QTL for the respective traits suggesting allelic sensitivity to temperature. Further fine mapping, complementation analyses and gene silencing are planned to identify candidate genes underlying phenotypic plasticity for age at maturity, fertility and growth.
Heredity, 2007
Empirical evidence is mounting to suggesting that genetic correlations between life-history trait... more Empirical evidence is mounting to suggesting that genetic correlations between life-history traits are environment specific. However, detailed knowledge about the loci underlying genetic correlations in different environments is scant. Here, we studied the influence of temperature (121C and 241C) on the genetic correlations between egg size, egg number and body mass in the nematode Caenorhabditis elegans. We used a quantitative trait loci (QTL) approach based on a genetic map with evenly spaced single nucleotide polymorphism markers in an N2 Â CB4856 recombinant inbred panel. Significant genetic correlations between various traits were found at both temperatures. We detected pleiotropic or closely linked QTL, which supported the negative correlation between egg size and egg number at 121C, the positive correlation across temperatures for body mass, and the positive correlation between body mass and egg size at 121C. The results indicate that specific loci control the covariation in these life-history traits and the locus control is prone to environmental conditions.
Genetics, 2010
Alternative splicing is considered a major mechanism for creating multicellular diversity from a ... more Alternative splicing is considered a major mechanism for creating multicellular diversity from a limited repertoire of genes. Here, we performed the first study of genetic variation controlling alternative splicing patterns by comprehensively identifying quantitative trait loci affecting the differential expression of transcript isoforms in a large recombinant inbred population of Caenorhabditis elegans, using a new generation of whole-genome very-high-density oligonucleotide microarrays. Using 60 experimental lines, we were able to detect 435 genes with substantial heritable variation, of which 36% were regulated at a distance (in trans). Nonetheless, we find only a very small number of examples of heritable variation in alternative splicing (22 transcripts), and most of these genes colocalize with the associated genomic loci. Our findings suggest that the regulatory mechanism of alternative splicing in C. elegans is robust toward genetic variation at the genome-wide scale, which is in striking contrast to earlier observations in humans.
Ecological Applications, 2007
This study aims to reveal whether complexity, namely, community and trophic structure, of chronic... more This study aims to reveal whether complexity, namely, community and trophic structure, of chronically stressed soil systems is at increased risk or remains stable when confronted with a subsequent disturbance. Therefore, we focused on a grassland with a history of four centuries of patchy contamination. Nematodes were used as model organisms because they are an abundant and trophically diverse group and representative of the soil food web and ecosystem complexity. In a field survey, a relationship between contaminants and community structures was established. Following, two groups of soil mesocosms from the field that differed in contamination level were exposed to different disturbance regimes, namely, to the contaminant zinc and a heat shock. The zinc treatment revealed that community structure is stable, irrespective of soil contamination levels. This implies that centuries of exposure to contamination led to adaptation of the soil nematode community irrespective of the patchy distribution of contaminants. In contrast, the heat shock had adverse effects on species richness in the highly contaminated soils only. The total nematode biomass was lower in the highly contaminated field samples; however, the biomass was not affected by zinc and heat treatments of the mesocosms. This means that density compensation occurred rapidly, i.e., tolerant species quickly replaced sensitive species. Our results support the hypothesis that the history of contamination and the type of disturbance determine the response of communities. Despite that ecosystems may be exposed for centuries to contamination and communities show adaptation, biodiversity in highly contaminated sites is at increased risk when exposed to a different disturbance regime. We discuss how the loss of higher trophic levels from the entire system, such as represented by carnivorous nematodes after the heat shock, accompanied by local biodiversity loss at highly contaminated sites, may result in detrimental effects on ecosystem functions.
Organismal development is the most dynamic period of the life cycle, yet we have only a rough und... more Organismal development is the most dynamic period of the life cycle, yet we have only a rough understanding of the dynamics of gene expression during adolescent transition. Here we show that adolescence in Caenorhabditis elegans is characterized by a spectacular expression shift of conserved and highly polymorphic genes. Using a high resolution time series we found that in adolescent worms over 10,000 genes changed their expression. These genes were clustered according to their expression patterns. One cluster involved in chromatin remodelling showed a brief up-regulation around 50 h post-hatch. At the same time a spectacular shift in expression was observed. Sequence comparisons for this cluster across many genotypes revealed diversifying selection. Strongly up-regulated genes showed signs of purifying selection in non-coding regions, indicating that adolescence-active genes are constrained on their regulatory properties. Our findings improve our understanding of adolescent transition and help to eliminate experimental artefacts due to incorrect developmental timing.