- Award ID(s):
- 1933738
- NSF-PAR ID:
- 10320683
- Date Published:
- Journal Name:
- Frontiers in cardiovascular medicine
- Volume:
- 8
- ISSN:
- 2297-055X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
Epigenetic mechanisms modulate gene expression levels during development, shaping how a single genome produces a diversity of phenotypes. Here, we begin to explore the epigenetic regulation of sexual dimorphism in pea aphids (Acyrthosiphon pisum) by focusing on microRNAs. Previous analyses of microRNAs in aphids have focused solely on females, so we performed deep sequencing of a sample containing early-stage males. We used this sample, plus samples from Genbank, to find 207 novel pea aphid microRNA coding loci. We localized microRNA loci to a chromosome-level assembly of the pea aphid genome and found that those on the X chromosome have lower overall expression compared to those on autosomes. We then identified a set of 19 putative male-biased microRNAs and found them enriched on the X chromosome. Finally, we performed protein-coding RNA-Seq of first instar female and male pea aphids to identify genes with lower expression in males. 10 of these genes were predicted targets of the 19 male-biased microRNAs. Our study provides the most complete set of microRNAs in the pea aphid to date and serves as foundational work for future studies on the epigenetic control of sexual dimorphism.more » « less
-
Sexual differentiation has long been considered “epigenetic”, although the meaning of that word has shifted over time. Here, we track the evolution of ideas about epigenetics in sexual differentiation, and identify principles that have emerged from recent studies. Experiments manipulating a particular epigenetic mechanism during neonatal life demonstrate a role for both histone acetylation and
DNA methylation in the development of sex differences in the brain and behaviour of rodents. In addition, hormone‐dependent sex differences in the number of neurones of a particular phenotype may be programmed by differences inDNA methylation early in life. Genome‐wide studies suggest that many effects of neonatal testosterone on the brain methylome do not emerge until adulthood, and there may be sex biases in the use of epigenetic marks that do not correlate with differences in gene expression. In other words, even when the transcription of a gene does not differ between males and females, the epigenetic underpinnings of that expression may differ. Finally, recent evidence suggests that sex differences in epigenetic marks may primarily serve to make gene expression more similar in males and females. We discuss the implications of these findings for understanding sex differences in susceptibility to disease, and point to recent conceptual and technical advances likely to influence the field going forward. -
Abstract Background Mammalian gonadal sex is determined by the presence or absence of a Y chromosome and the subsequent production of sex hormones contributes to secondary sexual differentiation. However, sex chromosome-linked genes encoding dosage-sensitive transcription and epigenetic factors are expressed well before gonad formation and have the potential to establish sex-biased expression that persists beyond the appearance of gonadal hormones. Here, we apply a comparative bioinformatics analysis on a pair of published single-cell datasets from mouse and human during very early embryogenesis—from two-cell to pre-implantation stages—to characterize sex-specific signals and to assess the degree of conservation among early acting sex-specific genes and pathways.
Results Clustering and regression analyses of gene expression across samples reveal that sex initially plays a significant role in overall gene expression patterns at the earliest stages of embryogenesis which potentially may be the byproduct of signals from male and female gametes during fertilization. Although these transcriptional sex effects rapidly diminish, sex-biased genes appear to form sex-specific protein–protein interaction networks across pre-implantation stages in both mammals providing evidence that sex-biased expression of epigenetic enzymes may establish sex-specific patterns that persist beyond pre-implantation. Non-negative matrix factorization (NMF) on male and female transcriptomes generated clusters of genes with similar expression patterns across sex and developmental stages, including post-fertilization, epigenetic, and pre-implantation ontologies conserved between mouse and human. While the fraction of sex-differentially expressed genes (sexDEGs) in early embryonic stages is similar and functional ontologies are conserved, the genes involved are generally different in mouse and human.
Conclusions This comparative study uncovers much earlier than expected sex-specific signals in mouse and human embryos that pre-date hormonal signaling from the gonads. These early signals are diverged with respect to orthologs yet conserved in terms of function with important implications in the use of genetic models for sex-specific disease.
-
Abstract The non‐consumptive effects of predation risk can strongly affect prey behaviour and fitness with emergent effects on community structure and ecosystem functioning. Prey may respond differently to predation risk based on key traits such as sex, but the influence of sex‐specific variation is typically explored in species with strong sexual dimorphism. However, sex‐specific responses to predation risk may arise even in prey species lacking sexual dimorphisms based on differences in the relative cost of reproduction.
Using a rocky intertidal food chain, we conducted a laboratory mesocosm experiment to explore sex‐specific responses of morphologically similar, reproductively mature prey (the snail
Nucella lapillus ) to predation risk and whether risk affected female fecundity.We found that predation risk suppressed prey growth only in males via effects on growth efficiency, suggesting that sex‐specific disparities may arise due to differences in the energy required for reproduction and/or the costs of mounting a physiological stress response. Moreover, while risk did not affect overall female fecundity, it eliminated the positive relationship between female size and fecundity observed in the absence of risk.
We hypothesize that these sex‐specific disparities arise due to differences in the energy required for reproduction and/or the costs of mounting a physiological stress response. Reproduction is likely more energetically costly for females than males, so females may display weaker antipredator responses in order to maintain energetic reserves needed for reproduction. Our results suggest that sex‐specific responses may be an important component of inter‐individual differences in prey responses to risk and influence prey population growth and demography even in species lacking sexual dimorphism.
A free
Plain Language Summary can be found within the Supporting Information of this article. -
Arkhipova, Irina (Ed.)Abstract Males and females of the same species share the majority of their genomes, yet they are frequently exposed to conflicting selection pressures. Gene regulation is widely assumed to resolve these conflicting sex-specific selection pressures, and although there has been considerable focus on elucidating the role of gene expression level in sex-specific adaptation, other regulatory mechanisms have been overlooked. Alternative splicing enables different transcripts to be generated from the same gene, meaning that exons which have sex-specific beneficial effects can in theory be retained in the gene product, whereas exons with detrimental effects can be skipped. However, at present, little is known about how sex-specific selection acts on broad patterns of alternative splicing. Here, we investigate alternative splicing across males and females of multiple bird species. We identify hundreds of genes that have sex-specific patterns of splicing and establish that sex differences in splicing are correlated with phenotypic sex differences. Additionally, we find that alternatively spliced genes have evolved rapidly as a result of sex-specific selection and suggest that sex differences in splicing offer another route to sex-specific adaptation when gene expression level changes are limited by functional constraints. Overall, our results shed light on how a diverse transcriptional framework can give rise to the evolution of phenotypic sexual dimorphism.more » « less