Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits

TLDR

DNA methylation changes can alter gene expression and be inherited, offering a potential source of heritable phenotypic variation independent of DNA sequence, yet quantifying their prevalence and impact on complex traits is confounded by DNA sequence polymorphisms. The study aimed to overcome this confounding by generating epigenetic recombinant inbred lines from two Arabidopsis thaliana parents with minimal DNA sequence differences but contrasting methylation profiles. These epiRILs were produced by crossing the two parents and advancing progeny through inbreeding to create a panel that segregates epialleles while keeping genetic background largely constant. The epiRIL panel exhibited approximately 30 % heritable variation in flowering time and plant height, with multiple parental epialleles stably inherited over at least eight generations, demonstrating that epigenetic variants can contribute to complex trait variation and should be integrated into population genetics studies.

Abstract

Loss or gain of DNA methylation can affect gene expression and is sometimes transmitted across generations. Such epigenetic alterations are thus a possible source of heritable phenotypic variation in the absence of DNA sequence change. However, attempts to assess the prevalence of stable epigenetic variation in natural and experimental populations and to quantify its impact on complex traits have been hampered by the confounding effects of DNA sequence polymorphisms. To overcome this problem as much as possible, two parents with little DNA sequence differences, but contrasting DNA methylation profiles, were used to derive a panel of epigenetic Recombinant Inbred Lines (epiRILs) in the reference plant Arabidopsis thaliana. The epiRILs showed variation and high heritability for flowering time and plant height ( approximately 30%), as well as stable inheritance of multiple parental DNA methylation variants (epialleles) over at least eight generations. These findings provide a first rationale to identify epiallelic variants that contribute to heritable variation in complex traits using linkage or association studies. More generally, the demonstration that numerous epialleles across the genome can be stable over many generations in the absence of selection or extensive DNA sequence variation highlights the need to integrate epigenetic information into population genetics studies.