# Mining Differentially Expressed Genes in the Marine Free-Living Flatworm Macrostomum lignano Under Aneuploidy-Driven Ploidy Changes

## TL;DR

This study explores how the flatworm Macrostomum lignano adapts to changes in genome copy number, revealing how gene expression shifts may support evolutionary success in polyploid organisms.

## Contribution

The study identifies specific genes and pathways involved in transcriptomic stability and phenotypic success in a successful neopolyploid flatworm model.

## Key findings

- 1308 genes showed nonlinear aneuploidy-induced transcriptional responses in M. lignano.
- Differentially expressed genes were enriched in pathways like mTOR signaling, ubiquitin-mediated proteolysis, and Hippo/Wnt.
- DV1_10 worms exhibited increased body size, enhanced cell proliferation, and higher viability compared to DV1_8 worms.

## Abstract

Whole-genome duplication (WGD) is a powerful evolutionary force, yet the mechanisms by which neopolyploids achieve transcriptomic stability and phenotypic success remain poorly understood. This study investigated the phenotypic and transcriptomic consequences of ploidy changes in the flatworm Macrostomum lignano, a “successful” neopolyploid model. We exploited two established sublines derived from the inbred DV1 line: the euploid DV1_8 (hidden tetraploid, SSL1L2) and the aneuploid DV1_10 (hidden hexaploid, SSL1L1L2L2). By integrating whole-genome sequencing (WGS)-informed normalization with RNA-seq analysis, we differentiated true regulatory shifts from gene-dosage effects. We revealed that while most genes scale linearly with ploidy, 1308 genes exhibited a nonlinear aneuploidy-induced transcriptional response. The remarkable trans-acting effects were observed across subgenome S encoded by disomic small chromosomes. Differentially expressed genes (DEGs) were enriched in pathways essential for homeostasis and growth: mTOR signaling, ubiquitin-mediated proteolysis, and the Hippo/Wnt pathways. Phenotypes of the DV1_10 worms exhibited increased body size, enhanced cell proliferation, and higher viability in comparison to the DV1_8 worms (60.25% vs. 21.5%). These findings suggest that M. lignano possesses mechanisms for dosage compensation to mitigate the deleterious effects of aneuploidy. Ultimately, this study demonstrates how genomic plasticity and rewiring of the transcriptome may facilitate the evolutionary success of animal neopolyploids.