Developmental phenomics suggests that H3K4 monomethylation catalyzed by Trr functions as a phenotypic capacitor

Abstract

How epigenetic modulators of gene regulation affect the development and evolution of animals has been difficult to ascertain. Despite the widespread presence of histone 3 lysine 4 monomethylation (H3K4me1) on enhancers, hypomethylation appears to have minor effects on animal development and viability. In this study, we performed quantitative, unbiased and multi-dimensional explorations of key phenotypes on Drosophila melanogaster with genetically induced hypomethylation. Hypomethylation reduced transcription factor enrichment in nuclear microenvironments, leading to reduced gene expression, and phenotypes outside of standard laboratory conditions. Our developmental phenomics survey further showed that H3K4me1 hypomethylation led to context-dependent changes in morphology, metabolism, and behavior. Therefore, H3K4me1 may contribute to phenotypic evolution as a phenotypic capacitor by buffering the effects of chance, genotypes and environmental conditions on transcriptional enhancers.

Rapid response of fly populations to gene dosage across development and generations

“…S3 ) might provide a molecular basis for the observed evolutionary changes. Importantly, these observations highlight the deep connections between multiple phenotypic layers of multicellular systems and argue for a broader ‘phenomics’ perspective (Gandara et al, 2022), instead of a strictly gene-centric view. In the future, exploring the interplay of metabolic and developmental networks could transform our understanding of evolution and development across variable ecologies (Miyazawa and Aulehla, 2018; Perkins et al, 2022), as such processes are fundamentally linked (White et al, 2022).…”

“…These results show that perturbation of one node of the developmental network, the bicoid dosage, can lead to profound organism-wide responses across multiple phenotypic scales. Importantly, these observations highlight the deep connections between multiple phenotypic layers of multicellular systems and argue for a broader 'phenomics' perspective 16 , instead of a strictly gene-centric view. Exploring the interplay of metabolic and developmental networks could transform our understanding of evolution and development across variable ecologies 5,15 , as such processes are fundamentally linked 70 .…”

“…Thousands of individual genes may contribute to phenotypes through expression in relevant cells (Boyle et al, 2017), and the contributions of each genetic variant to developmental fates are often small and challenging to measure (Frankel et al, 2011; Wood et al, 2014; Yengo et al, 2018). Therefore, it is essential to consider regulatory evolution and development both at the systems level and across populations (Gandara et al, 2022; Houle et al, 2010; Perkins et al, 2022). Clearly, approaches to elicit the relationships between different phenotypic layers and how these changes manifest across populations are needed to understand the evolution of developmental regulatory networks.…”