scholarly journals Heritability of DNA methylation in threespine stickleback (Gasterosteus aculeatus)

2020 ◽  
Author(s):  
Juntao Hu ◽  
Sara J. S. Wuitchik ◽  
Tegan N. Barry ◽  
Sean M. Rogers ◽  
Heather A. Jamniczky ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Architecture ◽  
Gasterosteus Aculeatus ◽  
Natural Populations ◽  
Threespine Stickleback ◽  
Phenotypic Change ◽  
Reduced Representation ◽  
Cpg Sites ◽  
Relative Contribution ◽  
Methylation Variation

AbstractEpigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTL) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that genetic variance explained an average of 24 to 35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. Finally, we detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes, as well as identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.

scholarly journals Heritability of DNA methylation in threespine stickleback (Gasterosteus aculeatus)

Genetics ◽  
2021 ◽  
Vol 217 (1) ◽  
Author(s):  
Juntao Hu ◽  
Sara J S Wuitchik ◽  
Tegan N Barry ◽  
Heather A Jamniczky ◽  
Sean M Rogers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Architecture ◽  
Gasterosteus Aculeatus ◽  
Additive Genetic Variance ◽  
Natural Populations ◽  
Threespine Stickleback ◽  
Phenotypic Change ◽  
Cpg Sites ◽  
Cis And Trans ◽  
Methylation Variation

Abstract Epigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTLs) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that additive genetic variance explained an average of 24–35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. We also detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes. Finally, we identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.

scholarly journals Persistent and plastic effects of temperature on DNA methylation across the genome of threespine stickleback ( Gasterosteus aculeatus )

2017 ◽  
Vol 284 (1864) ◽  
pp. 20171667 ◽  
Author(s):  
David C. H. Metzger ◽  
Patricia M. Schulte
Keyword(s):  
Dna Methylation ◽  
Time Scales ◽  
Gasterosteus Aculeatus ◽  
Natural Populations ◽  
Thermal Response ◽  
Thermal Acclimation ◽  
Threespine Stickleback ◽  
Multiple Time Scales ◽  
Acclimation Temperature ◽  
Multiple Time

Epigenetic mechanisms such as changes in DNA methylation have the potential to affect the resilience of species to climate change, but little is known about the response of the methylome to changes in environmental temperature in animals. Using reduced representation bisulfite sequencing, we assessed the effects of development temperature and adult acclimation temperature on DNA methylation levels in threespine stickleback ( Gasterosteus aculeatus ). Across all treatments, we identified 2130 differentially methylated cytosines distributed across the genome. Both increases and decreases in temperature during development and with thermal acclimation in adults increased global DNA methylation levels. Approximately 25% of the differentially methylated regions (DMRs) responded to both developmental temperature and adult thermal acclimation, and 50 DMRs were common to all treatments, demonstrating a core response of the epigenome to thermal change at multiple time scales. We also identified differentially methylated loci that were specific to a particular developmental or adult thermal response, which could facilitate the accumulation of epigenetic variation between natural populations that experience different thermal regimes. These data demonstrate that thermal history can have long-lasting effects on the epigenome, highlighting the role of epigenetic modifications in the response to temperature change across multiple time scales.

scholarly journals Epigenetics and Early Life Stress: Experimental Brood Size Affects DNA Methylation in Great Tits (Parus major)

2021 ◽  
Vol 9 ◽  
Author(s):  
Bernice Sepers ◽  
Jolijn A. M. Erven ◽  
Fleur Gawehns ◽  
Veronika N. Laine ◽  
Kees van Oers
Keyword(s):  
Dna Methylation ◽  
Life Stress ◽  
Early Life ◽  
Brood Size ◽  
Early Life Stress ◽  
Parus Major ◽  
Phenotypic Change ◽  
Phenotypic Traits ◽  
Reduced Representation ◽  
Cpg Sites

Early developmental conditions are known to have life-long effects on an individual’s behavior, physiology and fitness. In altricial birds, a majority of these conditions, such as the number of siblings and the amount of food provisioned, are controlled by the parents. This opens up the potential for parents to adjust the behavior and physiology of their offspring according to local post-natal circumstances. However, the mechanisms underlying such intergenerational regulation remain largely unknown. A mechanism often proposed to possibly explain how parental effects mediate consistent phenotypic change is DNA methylation. To investigate whether early life effects on offspring phenotypes are mediated by DNA methylation, we cross-fostered great tit (Parus major) nestlings and manipulated their brood size in a natural study population. We assessed genome-wide DNA methylation levels of CpG sites in erythrocyte DNA, using Reduced Representation Bisulfite Sequencing (RRBS). By comparing DNA methylation levels between biological siblings raised in enlarged and reduced broods and between biological siblings of control broods, we assessed which CpG sites were differentially methylated due to brood size. We found 32 differentially methylated sites (DMS) between siblings from enlarged and reduced broods, a larger number than in the comparison between siblings from control broods. A considerable number of these DMS were located in or near genes involved in development, growth, metabolism, behavior and cognition. Since the biological functions of these genes line up with previously found effects of brood size and food availability, it is likely that the nestlings in the enlarged broods suffered from nutritional stress. We therefore conclude that early life stress might directly affect epigenetic regulation of genes related to early life conditions. Future studies should link such experimentally induced DNA methylation changes to expression of phenotypic traits and assess whether these effects affect parental fitness to determine if such changes are also adaptive.

scholarly journals Epigenetic Potential and DNA Methylation in an Ongoing House Sparrow (Passer domesticus) Range Expansion

2020 ◽  
Author(s):  
Haley E. Hanson ◽  
Chengqi Wang ◽  
Aaron W. Schrey ◽  
Andrea L. Liebl ◽  
Rays H. Y. Jiang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Range Expansion ◽  
House Sparrow ◽  
Passer Domesticus ◽  
Adaptive Plasticity ◽  
Local Conditions ◽  
Reduced Representation ◽  
Immune Genes ◽  
Cpg Sites ◽  
Range Edge

AbstractDuring range expansions, epigenetic mechanisms may mediate phenotypic responses to environmental cues, enabling organisms to adjust to novel conditions at novel sites. Here, we predicted that the number of CpG sites within the genome, one form of epigenetic potential, would be important for success during range expansions because DNA methylation can modulate gene expression and hence facilitate adaptive plasticity. Previously, we found that this same form of epigenetic potential was higher in introduced compared to native populations of house sparrows (Passer domesticus) for two immune genes (Toll-like receptors 2A and 4). Here, we took a reduced-representation sequencing approach (ddRadSeq and EpiRadSeq) to investigate how CpG site number, as well as resultant DNA methylation, varied across five sites in the ∼70 year-old Kenyan house sparrow range expansion. We found that the number of CpG sites increased towards the vanguard of the invasion, even when accounting for variation in genetic diversity among sites. This pattern was driven by more losses of CpG sites towards the core of the invasion (the initial site of introduction). Across all sequenced loci, DNA methylation decreased but became more variable towards the range-edge. However, in the subset CpG sites proximal to mutated CpG sites, DNA methylation increased and variation declined. These results indicate that epigenetic potential influenced the Kenyan house sparrow range expansion, likely by providing greater phenotypic plasticity which is genetically assimilated as populations adapt to local conditions. Similar mechanisms might underlie the successes and failures of other natural and anthropogenic range expansions.

scholarly journals Genome-Wide DNA Methylation Patterns in Wild Samples of Two Morphotypes of Threespine Stickleback (Gasterosteus aculeatus)

2015 ◽  
Vol 32 (4) ◽  
pp. 888-895 ◽  
Author(s):  
Gilbert Smith ◽  
Carl Smith ◽  
John G. Kenny ◽  
Roy R. Chaudhuri ◽  
Michael G. Ritchie
Keyword(s):  
Dna Methylation ◽  
Gasterosteus Aculeatus ◽  
Threespine Stickleback ◽  
Genome Wide ◽  
Methylation Patterns

scholarly journals Combining epiGBS markers with long read transcriptome sequencing to assess differentiation associated with habitat in Reynoutria (aka Fallopia)

2020 ◽  
Author(s):  
Marta Robertson ◽  
Mariano Alvarez ◽  
Thomas van Gurp ◽  
Cornelis A. M. Wagemaker ◽  
Fahong Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Functional Divergence ◽  
Habitat Type ◽  
Clonal Plants ◽  
Habitat Types ◽  
Reduced Representation ◽  
Reduced Representation Bisulfite Sequencing ◽  
Long Read ◽  
Functional Relevance ◽  
Methylation Variation

SummaryDespite the limitations of genetic bottlenecks, several invasive species appear to thrive in non-native ranges with extremely low levels of sequence-based genetic variation. We previously demonstrated differentiation of DNA methylation to habitat types of the highly clonal, genetically depauperate Japanese knotweeds using anonymous markers, but the functional relevance of this DNA methylation variation is unknown. Here, we sequenced the full transcriptome combined with a reduced representation bisulfite sequencing approach, epigenotyping by sequencing (epiGBS), to characterize the association among DNA methylation, functional transcripts and the diverse habitat types occupied by the invasive Reynoutria species. We identified 50,435 putative transcripts overall, of which 48,866 were annotated with the NCBI NR database. Of these 17,872 (35%) and 16,122 (32%) transcripts shared sequence identity with Arabidopsis thaliana and Beta vulgaris, respectively. We found genetic differentiation by habitat type suggesting the action of selection and a marginal pattern of differentiation of DNA methylation among habitats, which appears to be associated with sequence differences. However, we found no individual methylation loci associated with habitat, limiting our ability to make functional interpretations. Regardless of the source of variation in DNA methylation, these changes may represent an important component of the response to environmental conditions, particularly in highly clonal plants, but more fine scale genomics analysis is required to test if DNA methylation variation in this system is responsible for functional divergence.

scholarly journals Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Kari Guderud ◽  
Line H. Sunde ◽  
Siri T. Flåm ◽  
Marthe T. Mæhlen ◽  
Maria D. Mjaavatten ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
Treatment Outcome ◽  
Pharmacological Action ◽  
Newly Diagnosed ◽  
Reduced Representation ◽  
Cpg Sites ◽  
Reduced Representation Bisulfite Sequencing ◽  
Before And After ◽  
Cell Type Specific

BackgroundMethotrexate (MTX) is the first line treatment of rheumatoid arthritis (RA), and methylation changes in bulk T cells have been reported after treatment with MTX. We have investigated cell-type specific DNA methylation changes across the genome in naïve and memory CD4+ T cells before and after MTX treatment of RA patients. DNA methylation profiles of newly diagnosed RA patients (N=9) were assessed by reduced representation bisulfite sequencing.ResultsWe found that MTX treatment significantly influenced DNA methylation levels at multiple CpG sites in both cell populations. Interestingly, we identified differentially methylated sites annotated to two genes; TRIM15 and SORC2, previously reported to predict treatment outcome in RA patients when measured in bulk T cells. Furthermore, several of the genes, including STAT3, annotated to the significant CpG sites are relevant for RA susceptibility or the action of MTX.ConclusionWe detected CpG sites that were associated with MTX treatment in CD4+ naïve and memory T cells isolated from RA patients. Several of these sites overlap genetic regions previously associated with RA risk and MTX treatment outcome.

scholarly journals Genetic divergence outpaces phenotypic evolution among threespine stickleback populations in old freshwater habitats

2019 ◽  
Author(s):  
Mark C Currey ◽  
Susan L Bassham ◽  
William A Cresko
Keyword(s):  
Genetic Divergence ◽  
Gasterosteus Aculeatus ◽  
Habitat Type ◽  
Threespine Stickleback ◽  
Ice Age ◽  
Phenotypic Change ◽  
Small Fish ◽  
Evolutionary Processes ◽  
Phenotypic Divergence ◽  
Freshwater Habitats

Abstract Species such as threespine stickleback (Gasterosteus aculeatus) that inhabit divergent selective environments and that have diversified on different time scales can be of value for understanding evolutionary processes. Here we synthesize high-resolution genotypic and phenotypic data to explore a largely unstudied distribution of threespine stickleback populations living in oceanic and freshwater habitats along coastal and inland regions of Oregon. Many inland aquatic habitats of Oregon remained unglaciated during the last ice age, meaning that some extant Oregon lake and river stickleback may have descended from freshwater populations established long before more well-studied, post-glacial freshwater populations. To address the degree of congruence between genetic and phenotypic divergence, we directly compared Oregon stickleback to much younger (post-glacial) Alaskan populations. We found phenotypic variation in Oregon stickleback to be primarily partitioned between oceanic and freshwater habitats, as has been documented in other stickleback systems. However, the main axis of genetic divergence was between coastal and inland regions regardless of habitat type. Furthermore, when comparing patterns between Oregon and Alaska we found similar levels of phenotypic divergence, but much greater genetic divergence among Oregon’s populations. The Oregon stickleback system therefore appears well suited for future studies linking genotypic and phenotypic change, further extending the utility of this small fish to provide general insights into evolutionary processes.

Abstract P366: Promoter Methylation of the Monoamine Oxidase a Gene is Associated With Fasting Plasma Glucose: A Monozygotic Twin Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
QIANG AN ◽  
Viola Vaccarino ◽  
Jack Goldberg ◽  
Jinying Zhao
Keyword(s):  
Dna Methylation ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Monozygotic Twin ◽  
Monoamine Oxidase A ◽  
Matched Pair ◽  
Cpg Sites ◽  
Matched Pair Analysis ◽  
Pair Analysis ◽  
Methylation Variation

Background: Epigenetic factors play an important role in complex diseases including diabetes. The monoamine oxidase A (MAOA) gene codes for the enzyme MAOA that plays a key role in the metabolism of neurotransmitters including dopamine, norepinephrine, and serotonin. These neurotransmitters are known to be involved in the pathogenesis of diabetes. No study has examined the association of MAOA methylation with fasting plasma glucose (FPG), independent of genetic factors. Objective: To examine whether MAOA promoter methylation variation is associated with FPG, independent of familiar factors. Methods: We studied 69 middle-aged, male-male monozygotic twin pairs drawn from the Vietnam Era Twin Registry. All twins were free of overt diabetes. DNA methylation at seven CpG sites in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. To examine whether MAOA promoter methylation variation influences FPG, we first calculated the intra-pair difference, defined as the difference in DNA methylation level at each CpG site between members of a twin pair. The intra-pair differences in FPG and other potential confounding factors were similarly calculated. We then conducted a matched pair analysis by regressing the intra-pair difference in FPG (dependent variable) on the intra-pair difference in DNA methylation level at each CpG site (independent variable), adjusting for intra-pair differences in body mass index (BMI), smoking pack-years, physical activity and depressive symptoms assessed by beck depression inventory (BDI). Multiple testing was corrected by the FDR p-value (or q-value) with a significant threshold of q<0.05. Results: The mean age of the twins was 55 years old. DNA methylation at the seven examined CpG sites varied from 1.6% to 19.0% with a mean methylation level of 5.0%. Intra-pair difference in FPG was significantly and positively correlated with intra-pair difference in methylation level at 3 out of the 7 CpG sites (r2 ranges 0.10 to 0.18, all P<0.025) as well as the mean methylation level (r2=0.10, p=0.026). Matched-pair analysis showed that methylation variation at 3 CpG sites was significantly associated with FPG (β ranges 1.83 to 2.33, all P<0.015), independent of BMI, smoking, physical activity and depressive symptoms. On average, a 1% increase in the intra-pair difference in mean methylation level was associated with a 2.21 mg/dl increase in the intra-pair difference in FPG (P=0.015). Conclusion: Methylation variation in the MAOA gene promoter is associated with FPG, independent of genetic and other clinical factors. This finding suggests a novel mechanism through which MAOA methylation variation, and perhaps its resulting changes in neurotransmitters, may contribute to diabetes.

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