Stress-mediated convergence of splicing landscapes in male and female rock doves

Abstract

Background: The process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes. Results: This study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, after subjecting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3'UTR (untranslated region) end of transcripts than the 5'UTR or coding regions. Conclusions: Our results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stressinduced reproductive dysfunction.

Genetic constraints in genes exhibiting splicing plasticity in facultative diapause

“…Growing evidence suggests that alternative splicing is an important axis of transcriptional variation contributing to phenotypic plasticity (Marden 2008 ; Verta and Jacobs 2022 ; Wright et al 2022 ). Large transcriptome-wide splicing differences between plastic phenotypes have recently been uncovered in a wide array of non-model species (Aamodt 2008 ; Grantham and Brisson 2018 ; Healy and Schulte 2019 ; Martin Anduaga et al 2019 ; Lang et al 2020 ; Thorstensen et al 2021 ; Steward et al 2022 ; Tian and Monteiro 2022 ). Differential splicing between plastic phenotypes is an important complement to whole-gene expression variation because it increases transcriptional complexity, control, and flexibility.…”

Specific expression of alternatively spliced genes in the turkey (Meleagris gallopavo) reproductive tract revealed their function in spermatogenesis and post-testicular sperm maturation

“…A few studies on AS have been reported in relation to bird reproduction ( Zhao et al, 2007 ; Huang et al, 2012 ; Lang et al, 2020 ; Rogers et al, 2021 , Sun et al, 2021 ). AS of testis-specific lactate dehydrogenase C ( LDHC ) and doublesex- and mab-3-related transcription factor 1 ( DMRT1 ) were reported for chicken and pigeon ( Zhao et al, 2007 ; Huang et al, 2012 ).…”

“…AS of testis-specific lactate dehydrogenase C ( LDHC ) and doublesex- and mab-3-related transcription factor 1 ( DMRT1 ) were reported for chicken and pigeon ( Zhao et al, 2007 ; Huang et al, 2012 ). NGS has been recently applied for the characterization of AS events during chicken male germline stem cell differentiation ( Sun et al, 2021 ), sex-specific aspects of the stress response in rock doves ( Lang et al, 2020 ) and the demonstration of the role of AS in the evolution of phenotypic complexity in birds ( Rogers et al, 2021 ). Nevertheless, the splicing profiles of genes involved in reproductive processes in birds have remained unexplored thus far.…”

Dynamic Gene Expression and Alternative Splicing Events Demonstrate Co-Regulation of Testicular Differentiation and Maturation by the Brain and Gonad in Common Carp

“…Although various alternative splicing events have been long to known to take place in both the gonad and brain, not much is known about the effects of alternative splicing on gonad development, with even lesser information about the difference in splicing between the gonad and brain. In vertebrates, various synchronous physiological events are required to regulate reproduction, and the molecular mechanism controlled by a comprehensive and interconnected biological system including the brain, the pituitary, and the gonads ( 13 ). However, information about the involvement of the HPG axis at the level of alternative splicing is limited, and even less is known about its effects at this level during testicular development.…”