The Epigenetics Dilemma

Abstract

This special issue of Genes demonstrates clearly that research in epigenetics has proceeded at a very rapid pace in the last decade. A wide range of techniques is available to those who endeavor studies in epigenetics and as long as there is a research budget, there remains today very few technical constraints. It is, for instance, conceivable, as demonstrated by Liu et al. in this special issue [1], to practically start from scratch to sequence and assemble the genome of any species, establish the epigenome, and perform integrative comparative approaches on both within the framework of a single publication. This would have been inconceivable only a couple of years ago. As a consequence, results presented in this issue and elsewhere make clear that this is a time of opportunity for epigenetics as its contours and impact are traced more and more clearly: the epigenome is demonstrated to be very plastic, it changes during development [2], but also, and in a different way, when exposed to external environmental cues. These changes occur sometimes within generations [3] and, in other cases, epigenetic plasticity occurs through generations [4,5], conveying parental effects of very different type (e.g., parental diet or hatchery environment).However, this plastic character of the epigenome makes it also difficult to draw general conclusions on how every epigenotype, genotype and phenotype are interrelated. In this issue, it is shown that phenotypic, and thus potentially gene expression changes, can precede epigenetic changes [3], or that they occur after the initial environmental stimulus [4,5]. It is also shown that epigenetic modifications can be associated with the magnitude of change in reaction norms of some but not all phenotypic traits [6]. In addition, even when considering the same bearer of epigenetic information (e.g., DNA methylation), different organisms show different types of DNA methylation (e.g., [1-6]) with potentially different types of phenotypic effects. Nevertheless, epigenetic changes do not occur randomly along the genome. In the two examples presented in this issue, environmentally induced epimutations were clearly enriched in the pathways of alert information and signaling: between 40% [5] and 66% [4] of differentially methylated regions (DMR) occurred in genes associated with signal transduction. This suggests that DMR are involved in the management of enduring and adequate stress response information.The current special issue of Genes thus reflects a peculiar situation for epigenetics research. We can accumulate, through hard work but eventually easily, large epigenomic data on a wide range of model and non-model organisms. We see clearly that environmental cues, especially stress, lead to specific changes in the epigenome that are accompanied by phenotypic modifications. We also see the relationship between epigenetic modifications and genomic plasticity (a large body of evidence in

Riding the merry‐go‐round of racial disparities in ADRD research

“…ADRD genetic ancestry research must grapple with notions of continental ancestry that are complicated by the human trafficking of persons from Africa during the Transatlantic Slave Trade, and the indentured servitude of groups racialized as Asian (e.g., Indian people in Trinidad and Guyana, Cantonese people in the United States ) 34 . Continental ancestry must look beyond fixed racialized categories to rethink terms like “admixture” that do not adequately capture continuous genetic makeup nor the traumatic implications of rape and forced procreation of persons who inhabited Africa, Asia, Australia, and the Americas at the colonial encounter producing “multiracial” persons later categorized by outsiders as “Mestije” or “Quadroon.” 11,35 These historic events inhibit distinguishing the impact of ancestry from intergenerational trauma and epigenetic change (within and across generations) 36 that current genetic risk scores and other algorithmic approaches fail to capture.

RECOMMENDATION #3: Learn the history of voluntary and forced migration to the United States and globally before invoking race or ancestry in ADRD research.

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“…34 Continental ancestry must look beyond fixed racialized categories to rethink terms like "admixture" that do not adequately capture continuous genetic makeup nor the traumatic implications of rape and forced procreation of persons who inhabited Africa, Asia, Australia, and the Americas at the colonial encounter producing "multiracial" persons later categorized by outsiders as "Mestije" or "Quadroon." 11,35 These historic events inhibit distinguishing the impact of ancestry from intergenerational trauma and epigenetic change (within and across generations) 36…”

Evolutionary feedback from the environment shapes mechanisms that generate genome variation

“…Germline epigenetic changes can be reversed, thus expanding rather than altering the range of environmental adaptation. But germline epigenetic changes also have been proposed as a form of phenotypic plasticity with the potential to become permanent (Grunau et al., 2020; Jablonka, 2017; Vernaz et al., 2022; West‐Eberhard, 2003).…”

Adaptação de >i<Helicoverpa armigera>/i< aos inibidores de peptidase de soja envolve uma alteração no padrão de expressão das serino peptidases e sugere um controle epigenético

“…Por outro lado, nem todas as alterações nos mecanismos epigenéticos produzem mudanças fenotípicas evidentes. Alguns estímulos ambientais causam alterações na estrutura da cromatina ou na regulação de genes (fenótipos moleculares) que podem ser transmitidos sigilosamente à prole (Grunau et al 2019). Assim, os fenótipos adquiridos podem ter efeitos adaptativos.…”

“…A arquitetura do promotor, por exemplo, é um dos fatores mais simples que controlam a produção de transcritos. Não obstante, é afetada muitas vezes pela presença de uma ou mais estruturas como: elementos de transposição (Klai et al 2020) (Grunau et al 2019). Estes fenômenos moleculares geralmente são mais compatíveis com a ideias de Lamarck.…”