ONT: Unveiling the Epigenetic Landscape across Generations


Understanding how organisms adapt and evolve over generations has long been a captivating scientific pursuit. Traditionally, this exploration focused on the role of DNA sequence variation, revealed through whole genome sequencing (WGS). However, recent advancements like Oxford Nanopore Technology (ONT) are enabling researchers to delve deeper, integrating the dynamic interplay between genes and the environment through epigenomics. This exciting new approach, combining WGS and epigenotyping across multiple generations of epigenetic selection, offers valuable insights into the complex mechanisms driving adaptation.

Oxford Nanopore Technology: A Game Changer in Sequencing

ONT has revolutionized the field of genomics by offering a portable, real-time sequencing platform. Unlike traditional methods, ONT utilizes nanopores, microscopic protein channels, to directly detect changes in electrical current as single DNA molecules pass through them. This makes ONT particularly well-suited for studying the combined effects of genetics and epigenetics in multigenerational selection experiments.

Epigenetics: Beyond the DNA Sequence

While DNA sequence plays a fundamental role in inheritance, it doesn't tell the whole story. Epigenetics refers to the heritable modifications to DNA that affect gene expression without altering the actual sequence. These modifications, including DNA methylation and histone acetylation, can be influenced by environmental factors, adding another layer of complexity to the process of adaptation.


Unveiling Epigenetic Selection Signatures: A Multifaceted Approach

By coupling WGS and epigenotyping using ONT across multiple generations of a selected population, researchers can gain a deeper understanding of how epigenetic selection shapes not just the genome, but also the epigenome.  Researchers choose a population undergoing epigenetic selection for a specific trait, such as disease resistance in plants or improved milk production in animals. 


This is not NeoDarwinian selection as no changes in the DNA sequence occurs.


DNA and epigenomic data are collected from individuals across multiple generations, typically focusing on germline cells like sperm or eggs to capture heritable changes. Different techniques, such as nanopore-based methylation profiling, are employed to assess the methylation status of DNA across the genome, revealing epigenetic modifications.

Unlocking the Secrets of Eoigenetic Adaptation

These regions may harbor genes directly involved in epigenetic adaptive traits or regulatory elements influencing their expression.

Investigating the correlation between specific DNA sequence variants and their associated epigenetic modifications can shed light on how these factors interact to influence gene expression.

By analyzing epigenetic modifications across generations even in the absence of NeoDarwinian selection pressure, researchers can explore the possibility of transgenerational epigenetic inheritance, where environmental experiences of one generation can impact the phenotypes of their descendants.


Evolutionary biology: Studying the interplay between genetics and epigenetics in natural populations can offer deeper insights into how organisms epigenetically adapt to changing environments over time. As research in this area continues to evolve, the integration of WGS and epigenotyping using ONT promises to revolutionize our understanding of adaptation providing a more comprehensive picture of how genes and their environment interact to shape the living world across generations.


Unveiling Epigenetic Evolution: A Multigenerational Study

The focus of this study was on a pig breed, where the researchers analyzed sperm samples from influential boars across 15 consecutive generations. ONT provided high-quality sequencing data, revealing both the complete genetic makeup (whole genome) and the methylation status of specific DNA regions (epigenotyping) for each sample. 

By analyzing this rich dataset, the researchers identified specific regions in the pig genome where methylation patterns changed significantly over generations. These changes suggest how the environment, not just DNA sequence variations, can influence gene expression and potentially contribute to epigenetic adaptation.

Furthermore, the study employed clustering techniques to group DNA methylation sites with similar evolutionary patterns. This analysis provided insights into the variation of epigenetic modifications across the genome and throughout generations. Additionally, the researchers explored the potential link between genetic and epigenetic changes, aiming to understand how these two mechanisms interact during epigenetic selection.

This groundbreaking work sheds light on the dynamic nature of epigenetic patterns and their potential role in evolution. By employing advanced sequencing technology, the researchers provide valuable data for developing statistical models to identify signatures of epigenetic selection. Ultimately, such models could lead to more comprehensive selection strategies that account for both genetic and non-genetic inheritance, contributing to significant advancements in breeding and genetic improvement.

Whole Genome Sequencing & Epigenetics: Challenging the Modern Synthesis

The modern synthesis (MS), a framework unifying Mendelian genetics and Darwinian evolution, has been losing ground as of late. Recent advancements like whole genome sequencing (WGS) and epigenotyping across multiple generations, facilitated by Oxford Nanopore Technology (ONT), are challenging core tenets of the modern synthesis.

WGS allows the complete reading of an organism's DNA, providing a detailed picture of its genetic makeup. Epigenotyping examines modifications to the DNA that don't change the underlying sequence as with evolution (MS) but can influence gene expression. By applying these combined techniques across multiple generations of epigenetic selection, researchers are uncovering new aspects of inheritance:

  • Non-genetic inheritance: Traditionally, only DNA variations (evolution) were considered heritable. Epigenetic modifications, however, can be passed down through generations, influencing phenotypes without altering the DNA sequence. This challenges the MS (evolution) sole dependence of DNA-based inheritance.

  • Transgenerational effects: Selection pressure applied to one generation can have lasting epigenetic effects on subsequent generations, even without any changes in the DNA sequence. This phenomenon is not accounted for in the modern synthesis, calling for revisions if not replacement of the MS (evolution).

Epigenetic selection signatures: Studying changes in methylation patterns across generations can reveal regions of the genome under epigenetic selection pressure. This information can be used to refine selection models and guide breeding programs, potentially leading to more efficient and targeted approaches.

These findings highlight the limitations of evolution (MS) in capturing the full complexity of inheritance and evolution. Integrating epigenetic information into evolutionary models will be crucial for a more complete understanding of how life epigenetically evolves and epigenetically adapts over time without evolution (MS).

Whole genome sequencing and epigenotyping for multiple generations of selection using Oxford Nanopore Technology


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