DNA methylation signatures of early-life adversity are exposure-dependent in wild baboons

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(11)

Опубликована: Март 5, 2024

The early-life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute these effects is DNA methylation. However, frequency and functional importance methylation in shaping on adult outcomes poorly understood, especially natural populations. Here, we integrate prospectively collected data fitness-associated variation early with estimates at 477,270 CpG sites 256 wild baboons. We find highly heterogeneous relationships between adulthood: aspects linked resource limitation (e.g., low-quality habitat, drought) are associated many more than other types environmental stressors low maternal social status). Sites enriched gene bodies putative enhancers, suggesting they functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, show that subset windows containing capable regulatory activity, that, for 88% drought-associated windows, enhancer activity methylation-dependent. Together, our results support idea patterns contain persistent signature environment. also indicate not all exposures leave equivalent mark suggest socioenvironmental time sampling likely be important. Thus, multiple mechanisms must converge explain fitness-related traits.

Язык: Английский

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DNA Methylation Dynamics Reflect Sex and Status Differences in Mortality Rates in a Polygynous Bat

Molecular Ecology, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

ABSTRACT Males of polygynous mammals often do not live as long females and, in some cases, exhibit evidence earlier senescence. Patterns DNA methylation (DNAm) have recently been used to predict chronological age mammals. Whether DNAm also changes a consequence survival and senescence is largely untested wild animals. In this study, we estimate mortality rates using recaptures 2700 greater spear‐nosed bats, Phyllostomus hastatus , over 34 years profiled for 300 adult bats. species, one male typically controls mating access group unrelated females. Bayesian analysis reveals that risk males 1.8 times females, comparison age‐associated differences indicates 1.4 faster than Therefore, even though the either sex predicted by common set sites, methylome more dynamic Sites associated with rate change are sensitive androgens enriched on X chromosome. hypermethylation promoters genes involved regulation metabolic processes. Unexpectedly, subordinate higher reproductively dominant dominants at dozens sites. Our results reveal social status reflected methylation, providing novel insights into mechanisms aging likely other animal populations.

Язык: Английский

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Social and early life determinants of survival from cradle to grave: A case study in wild baboons

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 152, С. 105282 - 105282

Опубликована: Июнь 15, 2023

Язык: Английский

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Embryonic temperature influences transcriptomic and methylation profiles in the liver of juvenile largemouth bass

Journal of Thermal Biology, Год журнала: 2025, Номер 128, С. 104073 - 104073

Опубликована: Фев. 1, 2025

Язык: Английский

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The interplay between epigenomic and transcriptomic variation during ecotype divergence in stickleback

BMC Biology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 5, 2025

Populations colonizing contrasting environments are likely to undergo adaptive divergence and evolve ecotypes with locally adapted phenotypes. While diverse molecular mechanisms underlying ecotype have been identified, less is known about their interplay degree of divergence. Here we integrated epigenomic transcriptomic data explore the interactions among gene expression, alternative splicing, DNA methylation, microRNA expression gauge extent which patterns at four levels aligned in a case postglacial between marine freshwater nine-spined sticklebacks (Pungitius pungitius). Despite significant genome-wide associations variation, found largely non-parallel across levels, predominantly nonoverlapping (ranging from 43.40 87.98%) sets differentially expressed, spliced methylated genes, candidate genes targeted by expressed miRNA ecotypes. Furthermore, variation different mechanisms, differential methylation splicing showing highest lowest ecotypes, respectively. Finally, enrichment associated methylation. Our results suggest nuanced relationship processes, alignment level masking relatively independent effects on level.

Язык: Английский

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Cost-effective solutions for high-throughput enzymatic DNA methylation sequencing

PLoS Genetics, Год журнала: 2025, Номер 21(5), С. e1011667 - e1011667

Опубликована: Май 22, 2025

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, development, geroscience, and medical genomics. While costs are decreasing, whole-genome profiling remains prohibitively expensive most population-scale studies, creating a need cost-effective, reduced representation approaches (i.e., assays that rely on microarrays, enzyme digests, or sequence capture to target subset of the genome). Most common whole genome techniques bisulfite conversion, which can damage resulting loss sequencing biases. Enzymatic methyl (EM-seq) was recently proposed overcome these issues, but thorough benchmarking EM-seq combined with strategies currently lacking. To address this gap, we optimized Targeted Methylation Sequencing protocol (TMS)—which profiles ~4 million CpG sites—for miniaturization, flexibility, multispecies use at cost ~USD 80. First, tested modifications increase throughput reduce cost, including increasing multiplexing, decreasing input, using enzymatic rather than mechanical fragmentation prepare DNA. Second, compared our TMS commonly used techniques, specifically Infinium MethylationEPIC BeadChip (n = 55 paired samples) 6 samples). In both cases, found strong agreement between technologies (R 2 0.97 0.99, respectively). Third, three non-human primate species (rhesus macaques, geladas, capuchins). We captured high percentage (mean 77.1%) targeted sites produced level estimates agreed those generated from 0.98). Finally, confirmed 1) epigenetic age 2) tissue-specific strongly recapitulated data versus other technologies. Altogether, will enable studies genome-wide levels across human species.

Язык: Английский

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Scars and PARs in a close relative

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(12)

Опубликована: Март 11, 2024

Язык: Английский

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DNA Methylation of PXDN Is Associated with Early-Life Adversity in Adult Mental Disorders

Biomolecules, Год журнала: 2024, Номер 14(8), С. 976 - 976

Опубликована: Авг. 9, 2024

Early-life adversity (ELA) is characterized by exposure to traumatic events during early periods of life, particularly involving emotional, sexual and/or physical adversities childhood. Mental disorders are strongly influenced environmental and lifestyle-related risk factors including ELA. However, the molecular link between ELA an adult mental disorder still not fully understood. Evidence emerging that long-lasting changes in epigenetic processes regulating gene expression, such as DNA methylation, play important role biological mechanisms linking disorders. Based on a recent study, we analyzed methylation specific CpG site within

Язык: Английский

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Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 24, 2024

ABSTRACT A major goal in evolutionary biology and biomedicine is to understand the complex interactions between genetic variants, epigenome, gene expression. However, causal relationships these factors remain poorly understood. mSTARR-seq, a methylation-sensitive massively parallel reporter assay, capable of identifying methylation-dependent regulatory activity at many thousands genomic regions simultaneously, allows for testing DNA methylation expression on region-by-region basis. Here, we developed multiplexed mSTARR-seq protocol assay naturally occurring human variation from 25 individuals sampled 10 localities Europe Africa. We identified 6,957 elements either unmethylated or methylated state, this set was enriched enhancer promoter annotations, as expected. The 58% modulated by methylation, which generally associated with decreased RNA Within our elements, used allele-specific analyses identify 8,020 sites effects regulation; further, found that 42.3% varied states. Sites exhibiting were GWAS EWAS implicating them disease. Compared datasets single European individual, uncovers dramatically more effects, highlighting importance including diverse assays aim processes.

Язык: Английский

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Cost-effective solutions for high-throughput enzymatic DNA methylation sequencing

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, geroscience, and medical genomics. While costs are decreasing, whole-genome profiling remains prohibitively expensive most population-scale studies, creating a need cost-effective, reduced representation approaches (i.e., assays that rely on microarrays, enzyme digests, or sequence capture to target subset of the genome). Most common whole genome techniques bisulfite conversion, which can damage resulting loss sequencing biases. Enzymatic methyl (EM-seq) was recently proposed overcome these issues, but thorough benchmarking EM-seq combined with strategies has not yet been performed. To do so, we optimized Targeted Methylation Sequencing protocol (TMS)-which profiles ∼4 million CpG sites-for miniaturization, flexibility, multispecies use at cost ∼$80. First, tested modifications increase throughput reduce cost, including increasing multiplexing, decreasing input, using enzymatic rather than mechanical fragmentation prepare DNA. Second, compared our TMS commonly used techniques, specifically Infinium MethylationEPIC BeadChip (n=55 paired samples) (n=6 samples). In both cases, found strong agreement between technologies (R² = 0.97 0.99, respectively). Third, three non-human primate species (rhesus macaques, geladas, capuchins). We captured high percentage (mean=77.1%) targeted sites produced level estimates agreed those generated from 0.98). Finally, applied profile age-associated variation two subsistence-level populations-the Tsimane lowland Bolivia Orang Asli Peninsular Malaysia-and age-methylation were strikingly similar reported income cohorts, despite known differences age-health relationships lifestyle contexts. Altogether, will enable studies genome-wide levels across human species.

Язык: Английский

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