BACKGROUND: Recent studies have demonstrated that prolonged sperm storage adversely affects offspring through epigenetics, yet its broader effects on other molecular levels such as transcription and proteomics in progeny have been rarely explored. RESULTS: We employed comprehensive multi-omics approaches to uncover storage-induced epigenetic changes in sperm and their effects on embryonic development and offspring health. Sperm from common carp (Cyprinus carpio) was stored in vitro in artificial seminal plasma for 14 days, and the impacts of storage on functional properties of sperm and progeny development were investigated. We combined DNA methylome, transcriptomic and proteomic data to elucidate the potential mechanisms by which sperm storage influences progeny development. Prolonged in vitro storage significantly reduced sperm motility and fertilising ability which coincided with changes in the DNA methylation pattern. Integrated analyses of the offspring DNA methylome, comparative transcriptomics and cardiac performance measurements revealed storage-induced alterations of genes associated with nervous system development, myocardial morphogenesis and cellular responses to stimuli. Proteomic analyses showed that in addition to visual perception and nervous system function, pathways of the immunity system were also enriched. Results provide strong evidence of the epigenetic inheritance of the offspring's performances when short-term stored sperm was used for fertilisation. CONCLUSIONS: Short-term sperm storage induces heritable molecular and phenotypic changes in offspring, raising concerns over the potential intergenerational consequences of assisted reproductive practices in aquaculture and possibly other vertebrates.
- Keywords
- Epigenetic inheritance, Epigenetics, Fish sperm, Offspring development, Sperm ageing,
- MeSH
- Embryonic Development * MeSH
- Epigenesis, Genetic MeSH
- Carps * genetics physiology embryology MeSH
- DNA Methylation MeSH
- Multiomics MeSH
- Proteomics MeSH
- Spermatozoa * physiology metabolism MeSH
- Transcriptome MeSH
- Semen Preservation * adverse effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Seed production is facing a three-fold challenge: ensuring food security, maintaining sustainability, and adapting to climate change. Although most efforts have focused on genetic breeding and crop management, additional levers need to be explored to optimize plant tolerance to the accelerating climate change. A groundbreaking approach will be to capitalize on the ability of plants to naturally adjust their responses to fluctuating environments during the crop cycle and transmit stress-induced information to the next generation(s). This viewpoint aims at highlighting the potential application of maternal stress memory as a priming strategy to produce primed seedlots. This requires identifying the priming conditions among stress memory scenarios, defined according to the starting point of the new generation within the plant, that is, the fertilization. If the contribution of stress-induced epigenetic-associated mechanisms in inheritance patterns to promote germination and early growth development has been evidenced, the whole picture is not fully understood. Further investigations are required to characterize the maternally inherited plant stress imprints leading to higher stress tolerance of seedlots. Detailed characterization of the mechanisms of stress-induced maternally heritable seed traits could provide novel targets for the seed industry and open new avenues to deploy the potential of maternal stress memory for enhancing seed performances.
- Keywords
- acclimation, epigenetics, germination, intra/inter/transgenerational memory, maternal, seed priming, seeds, stress memory,
- MeSH
- Epigenesis, Genetic * MeSH
- Stress, Physiological MeSH
- Germination genetics MeSH
- Climate Change MeSH
- Seeds * genetics physiology growth & development MeSH
- Plant Breeding MeSH
- Crops, Agricultural * genetics physiology growth & development MeSH
- Publication type
- Journal Article MeSH
Phenotypic diversification within pathogen populations can enhance survival in stressful environments, broaden niche colonization, and expand the ecological range of infectious diseases due to emerging collective pathogenicity characteristics. We describe a gene regulatory network property in the opportunistic pathogen Pseudomonas aeruginosa that generates diversity of gene expression and pathogenicity behavior at the single-cell level and that is stabilized by epigenetic cellular memory. The resulting heterogeneity in the expression of the glpD gene-an indicator of host-derived glycerol metabolism and intra-host presence-shapes adaptive processes that are subject to natural selection. Our work on how epigenetics generates phenotypic variation in response to the environment and how these changes are inherited to the next generation provides insights into phenotypic diversity and the emergence of unique functionalities at higher levels of organization. These could be crucial for controlling infectious disease outcomes.
- Keywords
- GlpD, Pseudomonas aeruginosa, epigenetic memory, glycerol metabolism, single-cell,
- MeSH
- Bacterial Proteins genetics metabolism MeSH
- Epigenetic Memory MeSH
- Epigenesis, Genetic * MeSH
- Phenotype MeSH
- Gene Regulatory Networks MeSH
- Host-Pathogen Interactions * genetics MeSH
- Pseudomonas Infections microbiology MeSH
- Pseudomonas aeruginosa * genetics pathogenicity MeSH
- Gene Expression Regulation, Bacterial MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Bacterial Proteins MeSH
BACKGROUND AND AIMS: Climate change threatens plant species, potentially exceeding their adaptive capacities. Plants may adapt to rapid environmental changes through transgenerational plasticity (TGP), where adaptive traits are passed to their offspring via proteins, hormones, and epigenetic modifications like DNA methylation. The extent of TGP and its ecological implications may differ between sexual and clonal reproductive modes due to differences in the inheritance of DNA methylation and provisioning. However, it remains unclear whether TGP differs between these reproductive modes and the role of DNA methylation. Addressing this gap is crucial, as higher TGP in clonal propagation could compensate for low genetic variation and help these plants in adapting to rapid environmental changes. METHODS: We assessed the adaptive potential of woodland strawberry (Fragaria vesca), a widely distributed herb with both clonal and sexual reproduction, in response to environmental conditions expected by the end of the 21st century: a temperature rise of 4 °C, a 400 ppm rise in atmospheric CO2, and periodic droughts. We quantified ecologically relevant phenotypic traits and examined whole-genome DNA methylation patterns in parents and their clonal and sexual offspring. KEY RESULTS: We found evidence for TGP induced by the parental environment, with a stronger overall effect observed in clonal compared to sexual offspring. Specifically, parental exposure to current temperature and CO2 conditions prompted adaptive TGP, particularly in clonal offspring. Additionally, adaptive TGP was observed exclusively in clonal offspring in response to a combination of elevated parental temperature and drought conditions. Finally, we found a higher inheritance of DNA methylation marks in clonal than sexual offspring. CONCLUSIONS: These results suggest that while TGP via DNA methylation can influence clonal plant adaptation to future conditions, it remains uncertain whether this influence will consistently result in adaptive outcomes. Moreover, TGP would likely be more important in clonal than sexual reproduction.
The epigenome is the suite of interacting chemical marks and molecules that helps to shape patterns of development, phenotypic plasticity and gene regulation, in part due to its responsiveness to environmental stimuli. There is increasing interest in understanding the functional and evolutionary importance of this sensitivity under ecologically realistic conditions. Observations that epigenetic variation abounds in natural populations have prompted speculation that it may facilitate evolutionary responses to rapid environmental perturbations, such as those occurring under climate change. A frequent point of contention is whether epigenetic variants reflect genetic variation or are independent of it. The genome and epigenome often appear tightly linked and interdependent. While many epigenetic changes are genetically determined, the converse is also true, with DNA sequence changes influenced by the presence of epigenetic marks. Understanding how the epigenome, genome and environment interact with one another is therefore an essential step in explaining the broader evolutionary consequences of epigenomic variation. Drawing on results from experimental and comparative studies carried out in diverse plant and animal species, we synthesize our current understanding of how these factors interact to shape phenotypic variation in natural populations, with a focus on identifying similarities and differences between taxonomic groups. We describe the main components of the epigenome and how they vary within and between taxa. We review how variation in the epigenome interacts with genetic features and environmental determinants, with a focus on the role of transposable elements (TEs) in integrating the epigenome, genome and environment. And we look at recent studies investigating the functional and evolutionary consequences of these interactions. Although epigenetic differentiation in nature is likely often a result of drift or selection on stochastic epimutations, there is growing evidence that a significant fraction of it can be stably inherited and could therefore contribute to evolution independently of genetic change.
- Keywords
- DNA methylation, epigenetics, gene–environment interactions, natural populations, transgenerational effects, transposable elements,
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) β, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.
- Keywords
- GWAS, Mendelian randomization, early-onset colorectal cancer, genetics, risk factors,
- MeSH
- Genome-Wide Association Study * MeSH
- Adult MeSH
- Genetic Predisposition to Disease * MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms * genetics epidemiology MeSH
- Humans MeSH
- Mendelian Randomization Analysis * MeSH
- Risk Factors MeSH
- Case-Control Studies MeSH
- Age of Onset MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
Due to the accelerating climate change, it is crucial to understand how plants adapt to rapid environmental changes. Such adaptation may be mediated by epigenetic mechanisms like DNA methylation, which could heritably alter phenotypes without changing the DNA sequence, especially across clonal generations. However, we are still missing robust evidence of the adaptive potential of DNA methylation in wild clonal populations. Here, we studied genetic, epigenetic and transcriptomic variation of Fragaria vesca, a predominantly clonally reproducing herb. We examined samples from 21 natural populations across three climatically distinct geographic regions, as well as clones of the same individuals grown in a common garden. We found that epigenetic variation was partly associated with climate of origin, particularly in non-CG contexts. Importantly, a large proportion of this variation was heritable across clonal generations. Additionally, a subset of these epigenetic changes affected the expression of genes mainly involved in plant growth and responses to pathogen and abiotic stress. These findings highlight the potential influence of epigenetic changes on phenotypic traits. Our findings indicate that variation in DNA methylation, which can be environmentally inducible and heritable, may enable clonal plant populations to adjust to their environmental conditions even in the absence of genetic adaptation.
- Keywords
- adaptation, climate change, clonal plant, ecological epigenetics, environmentally induced epigenetic variation, inheritance, natural populations, transposons,
- MeSH
- Clone Cells MeSH
- Epigenesis, Genetic MeSH
- Phenotype MeSH
- Fragaria * genetics MeSH
- Humans MeSH
- DNA Methylation * genetics MeSH
- Plants genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Recent advancements in the understanding of how sperm develop into offspring have shown complex interactions between environmental influences and genetic factors. The past decade, marked by a research surge, has not only highlighted the profound impact of paternal contributions on fertility and reproductive outcomes but also revolutionized our comprehension by unveiling how parental factors sculpt traits in successive generations through mechanisms that extend beyond traditional inheritance patterns. Studies have shown that offspring are more susceptible to environmental factors, especially during critical phases of growth. While these factors are broadly detrimental to health, their effects are especially acute during these periods. Moving beyond the immutable nature of the genome, the epigenetic profile of cells emerges as a dynamic architecture. This flexibility renders it susceptible to environmental disruptions. The primary objective of this review is to shed light on the diverse processes through which environmental agents affect male reproductive capacity. Additionally, it explores the consequences of paternal environmental interactions, demonstrating how interactions can reverberate in the offspring. It encompasses direct genetic changes as well as a broad spectrum of epigenetic adaptations. By consolidating current empirically supported research, it offers an exhaustive perspective on the interwoven trajectories of the environment, genetics, and epigenetics in the elaborate transition from sperm to offspring.
- Keywords
- environmental pollution, epigenetic changes, genetic infertility, semen quality, transgenerational effects,
- MeSH
- Epigenesis, Genetic MeSH
- Phenotype MeSH
- Humans MeSH
- Disease Susceptibility MeSH
- Reproduction genetics MeSH
- Semen * MeSH
- Spermatozoa * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Nucleolar dominance (ND) is selective epigenetic silencing of 35-48S rDNA loci. In allopolyploids, it is frequently manifested at the cytogenetic level by the inactivation of nucleolar organiser region(s) (NORs) inherited from one or several evolutionary ancestors. Grasses are ecologically and economically one of the most important land plant groups, which have frequently evolved through hybridisation and polyploidisation events. Here we review common and unique features of ND phenomena in this monocot family from cytogenetic, molecular, and genomic perspectives. We highlight recent advances achieved by using an allotetraploid model grass, Brachypodium hybridum, where ND commonly occurs at a population level, and we cover modern genomic approaches that decipher structural features of core arrays of NORs.
- Keywords
- 35S rRNA genes, allopolyploidy, epigenetics, grasses, nucleolar dominance, regulation of gene expression,
- MeSH
- Cell Nucleolus * genetics MeSH
- Genes, rRNA MeSH
- Poaceae genetics MeSH
- Nucleolus Organizer Region * MeSH
- DNA, Ribosomal genetics MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- DNA, Ribosomal MeSH
Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different parts of the genome. Most research so far has shed light on the puzzle pieces at these levels. This article, however, attempts an integrative approach to genome expression regulation incorporating these different layers. Under environmental stress or during cell development, differentiation towards specialized cell types, or to dysfunctional tumor, the cell nucleus seems to react as a whole through coordinated changes at all levels of control. This implies the need for a framework in which biological, chemical, and physical manifestations can serve as a basis for a coherent theory of gene self-organization. An international symposium held at the Biomedical Research and Study Center in Riga, Latvia, on 25 July 2022 addressed novel aspects of the abovementioned topic. The present article reviews the most recent results and conclusions of the state-of-the-art research in this multidisciplinary field of science, which were delivered and discussed by scholars at the Riga symposium.
- Keywords
- database pattern analysis, dynamic genome organization, epigenetic interactions, fluorescence microscopy, gene activity oscillations, heterochromatin and self-organization, nucleotide k-mers, organizational and functional networks, topological genome analysis, transposon-effected regulation,
- MeSH
- Cell Differentiation genetics MeSH
- Cell Nucleus * metabolism MeSH
- Genome * MeSH
- Publication type
- Congress MeSH
- Review MeSH
