Divergence of X-linked trans regulatory proteins and the misexpression of gene targets in sterile Drosophila pseudoobscura hybrids

Alwyn C Go,Alberto Civetta

doi:10.1186/s12864-021-08267-w

Abstract

BackgroundThe genetic basis of hybrid incompatibilities is characterized by pervasive cases of gene interactions. Sex chromosomes play a major role in speciation and X-linked hybrid male sterility (HMS) genes have been identified. Interestingly, some of these genes code for proteins with DNA binding domains, suggesting a capability to act as trans-regulatory elements and disturb the expression of a large number of gene targets. To understand how interactions between trans- and cis-regulatory elements contribute to speciation, we aimed to map putative X-linked trans-regulatory elements and to identify gene targets with disrupted gene expression in sterile hybrids between the subspecies Drosophila pseudoobscura pseudoobscura and D. p. bogotana.ResultsWe find six putative trans-regulatory proteins within previously mapped X chromosome HMS loci with sequence changes that differentiate the two subspecies. Among them, the previously characterized HMS gene Overdrive (Ovd) had the largest number of amino acid changes between subspecies, with some substitutions localized within the protein’s DNA binding domain. Using an introgression approach, we detected transcriptional responses associated with a sterility/fertility Ovd allele swap. We found a network of 52 targets of Ovd and identified cis-regulatory effects among target genes with disrupted expression in sterile hybrids. However, a combined analysis of polymorphism and divergence in non-coding sequences immediately upstream of target genes found no evidence of changes in candidate regulatory proximal cis-elements. Finally, peptidases were over-represented among target genes.ConclusionsWe provide evidence of divergence between subspecies within the DNA binding domain of the HMS protein Ovd and identify trans effects on the expression of 52 gene targets. Our results identify a network of trans-cis interactions with possible effects on HMS. This network provides molecular evidence of gene × gene incompatibilities as contributors to hybrid dysfunction.

Highlights

The genetic basis of hybrid incompatibilities is characterized by pervasive cases of gene interactions
Within species, GFZF exerts its effect as a transcriptional coactivator [17], and in hybrids between species HMR mislocalizes to sites normally occupied by GFZF with this mislocalization being rescuable by the reduced expression of the gfzf allele [18]
Six proteins within X‐linked hybrid male sterility (HMS) loci are candidate trans‐regulatory factors with fixed amino acid changes between subspecies We found ten protein coding genes in the right arm of the X chromosome (XR) and 203 within the left arm (XL) HMS loci

Summary

Introduction

The genetic basis of hybrid incompatibilities is characterized by pervasive cases of gene interactions. Sex chromosomes play a major role in speciation and X-linked hybrid male sterility (HMS) genes have been identified. Within species, GFZF exerts its effect as a transcriptional coactivator [17], and in hybrids between species HMR mislocalizes to sites normally occupied by GFZF with this mislocalization being rescuable by the reduced expression of the gfzf allele [18]. This example highlights the importance of gene × gene interactions on the onset of hybrid dysfunction and speciation. Genome-wide surveys have supported the role of complex systems of epistasis on the onset of hybrid incompatibility phenotypes [19,20,21,22]

Objectives

Methods

Results

Discussion

Conclusion