# Network architecture of transcriptomic stress responses in zebrafish embryos

## TL;DR

This study shows how zebrafish genes respond to stress by examining their positions in protein interaction networks, revealing both conserved and stress-specific patterns.

## Contribution

The study links stressor-specific gene expression patterns to PPI network positions in zebrafish embryos, revealing conserved and unique response mechanisms.

## Key findings

- Stress response genes are more centrally located in the PPI network.
- Heat stress affects both central and peripheral genes, while UV stress affects central to intermediate genes.
- Differentially expressed genes across network positions lead to similar phenotypic outcomes.

## Abstract

Protein-protein interaction (PPI) network topology can contribute to explaining fundamental properties of genes, from expression levels to evolutionary constraints. Genes central to a network are more likely to be both conserved and highly expressed, whereas genes that are able to evolve in response to selective pressures but expressed at lower levels are located on the periphery of the network. The stress response is likewise thought to be conserved and its associated genes highly expressed, however, experimental evidence for these patterns is limited. Therefore, we examined here whether the transcriptomic response to two environmental stressors (heat, UV, and their combination) is related to PPI architecture in zebrafish (Danio rerio) embryos. We show that stress response genes are situated more centrally in the PPI network. The transcriptomic response to heat was located in both central and peripheral positions, whereas UV response transcripts occupied central to intermediate positions. Network position was further linked to the magnitude of fold changes of genes and number of their associated phenotype GO terms. Across treatments, differentially expressed genes in different parts of the network affected identical phenotypes. Our results indicate that the zebrafish stress response is considered conserved but also have stressor-specific aspects. These properties can aid in better understanding the organismal response to diverse and co-occurring stressors. Given the speed of contemporary changes in aquatic ecosystems, our approach can aid in identifying novel key regulators of the systemic response to specific stressors.

Understanding how genes interact with each other within networks can reveal important insights into cellular activity and evolution. Generally, genes that play a central role in networks tend to be both conserved and highly active, while genes on the outskirts are more adaptable but less active. We investigated how zebrafish genes respond to different stressors (heat, UV radiation, and their combination), and how these responses relate to their positions in the network. Our findings show that genes involved in stress responses are central in the network. Heat stress additionally causes activity changes in genes at the edges, while UV stress additionally influences intermediate genes. Despite different stressors affecting genes in various network locations, the impacted genes lead to similar physical traits in the zebrafish. This suggests that while the stress response is largely conserved, there are also unique aspects depending on the specific stressor. Our approach can help identify new key genes that regulate how zebrafish respond to environmental changes, providing valuable insights for understanding how aquatic organisms adapt to rapid environmental shifts.