Interaction of Male Specific Lethal complex and genomic imbalance on global gene expression in Drosophila

Shuai Zhang,Cheng Huang,Yu Tian,Lin Sun,Ludan Zhang,Lijia Yuan,Ruixue Wang,Haizhu Qi

doi:10.1038/s41598-021-99268-y

Abstract

The inverse dosage effect caused by chromosome number variations shows global consequences in genomic imbalance including sexual dimorphism and an X chromosome-specific response. To investigate the relationship of the MSL complex to genomic imbalance, we over-expressed MSL2 in autosomal and sex chromosomal aneuploids, and analyzed the different transcriptomes. Some candidate genes involved in regulatory mechanisms have also been tested during embryogenesis using TSA-FISH. Here we show that the de novo MSL complex assembled on the X chromosomes in females further reduced the global expression level on the basis of 2/3 down-regulation caused by the inverse dosage effect in trisomy through epigenetic modulations rather than induced dosage compensation. Plus, the sexual dimorphism effect in unbalanced genomes was further examined due to the pre-existing of the MSL complex in males. All these results demonstrate the dynamic functions of the MSL complex on global gene expression in different aneuploid genomes.

Highlights

The inverse dosage effect caused by chromosome number variations shows global consequences in genomic imbalance including sexual dimorphism and an X chromosome-specific response
To further determine whether the newly assembled MSL complex induces dosage compensation of X chromosome genes in aneuploid females, we examined the global expression and made ratio distributions of gene expression in trisomy 2 left arm (2L) and MSL2-trisomy 2L compared with the normal diploid (Fig. 1B)
Selected genes were used to verify the RNA-seq results (Table S1 and S2). This analysis showed that, the gray line of the trisomy 2L female/diploid female is centered around a ratio of 0.67, which is caused by the inverse dosage effect when the 2L chromosome segment is increased to three copies, and the red line with over-expressed MSL complex does not show any movement to the right side, on the contrary, it produces more down-regulations to the left side with a peak around 0.45 (Fig. 1B; Kolmogorov–Smirnov (K-S) test P = 3.27e−9)

Summary

Introduction

The inverse dosage effect caused by chromosome number variations shows global consequences in genomic imbalance including sexual dimorphism and an X chromosome-specific response. The sexual dimorphism effect in unbalanced genomes was further examined due to the pre-existing of the MSL complex in males All these results demonstrate the dynamic functions of the MSL complex on global gene expression in different aneuploid genomes. Variations in the number of chromosomes can generally be divided into two categories, euploid variation and aneuploid variation[1,2] The former refers to the increase or decrease of the entire chromosome complement, which produces polyploids or h aploids[2]. An inverse dosage effect acts across the genome, on the varied chromosomes[9,24,25] This is the reason why the expression of most genes in aneuploidy tends to decrease with the increase of selected gene dosage[9,19,26,27]. The dosage compensation mechanism compensates for differences of sex chromosomes, and occurs for autosomal r egions[34]

Methods

Results

Conclusion