| Symposium proposal |
| Organizer: | Zhen-Xia Chen (Huazhong Agricultural University) |
Sexually reproducing animals usually demonstrate remarkable differences between females and males in morphological, physiological and behavioral phenotypes. Studying the evolution and underlying mechanisms of such sex differences is important not only for understanding gene regulation and evolution, but also for the application to animal reproduction and pest control.
Dr. Oliver and Dr. Dowling are well-known experts working on sex differences for over a decade. They will bring important findings and insights to the symposium.
Dr. Oliver works on sex-biased gene expression in flies. His long-term goal is to develop predictive models of gene function with a specific focus on sex differentiation in the germline. His approach relies on high-throughput techniques used to profile biological processes such as expression, promoter occupancy, and chromatin status, in conjunction with computational analysis and genetics.
Dr. Dowling works on the genotypic contributions of mitochondrial and nuclear genomes (and their interactions) to sex differences in organismal life history, from reproductive performance to longevity. Their research demonstrated that the maternal inheritance of the mitochondria is bad news for males but females. Their key tool is genetic strains of fruit flies in which different mitochondrial DNA haplotypes have been introgressed alongside a diverse set of nuclear DNA backgrounds. |
S3-1
Sex and the single cell
Brian Oliver1
1National Institutes of Health
Drosophila melanogaster sex is determined in each cell of the young embryo based on the number of X chromosomes present. Wildtype XX cells are female and XY cells are male. Later in development cell-cell and organ-organ signaling provide additional cues for sex differences in gene expression, morphology, physiology, and behavior. Gene expression profiling of whole flies and isolated tissues show extensive sexual dimorphism. As part of the Fly Cell Atlas consortium, we have now explored expression of >500K individual cells (nuclei) and explored sexual dimorphism at the single cell level. In non-reproductive tissues, we find extensive dimorphic gene expression in cells expressing the DMRT transcription factor, Doublesex. Cell types showing dimorphic expression include those found in essentially every major organ. In reproductive tissues, the dividing somatic and germline cells show sex-specific trajectories, and at least in males, chromosome-wide transcriptional effects. These results highlight the value of single cell resolution in studying sex differences and the importance of examining females and males separately regardless of the tissue or organ under study.
S3-2
Mitochondria and the evolution of sex differences
Damian Dowling1
1School of Biological Science, Monash University
In theory, maternal inheritance of mitochondria creates a sex-specific selective sieve, enabling the accumulation of mutations in the mitochondrial DNA that are harmful to males, when these same mutations are neutral, beneficial or only slightly deleterious to females. This has been called the Mother’s Curse hypothesis, and the subsequent male-biased mutation loads that accrue within the mitochondrial genome could in theory shape the evolution of sex differences in expression of key life-history traits. Although theory outlining this hypothesis is well established, there have been relative few studies tests to explicitly test its key predictions, and thus whether or not Mother’s Curse is a pervasive phenomenon affecting the life-histories of sexually reproducing metazoans remains controversial. I will outline the predictions of the hypothesis and describe recent experiments from our lab group that explore the capacity for sex-specific and sexually-antagonistic mitochondrial mutations to affect key physiological and life-history traits in the fruit fly, Drosophila melanogaster. I will describe complex effects on physiology and life-history associated with one particular naturally-occurring mitochondrial haplotype in this species, which carries a mutation previously reported to confer male infertility. I will outline the evolutionary implications of these studies, and highlight future research questions that require resolution before we can fully understand the implications of Mother’s Curse to the evolution of male life-histories.
S3-3
X chromosome genes that contribute to sex differences in disease
Arthur P. Arnold1
1University of California, Los Angeles
Many diseases show sex differences in incidence or progression, suggesting that one sex has inherent biological factors that protect from or exacerbate disease.
Historically the root causes of all sex differences in tissue phenotypes were thought to be the gonadal hormones. The advent of specialized mouse models has uncovered non-hormonal origins of sex bias in disease, caused by inherent inequality of XX vs. XY sex chromosomes. For example, the Four Core Genotypes and XY* models allow the investigator to compare mice with different sex chromosomes, but with the same type of gonad. Use of these mouse lines in several models of disease has now progressed far enough that specific X or Y genes have been identified that give rise to molecular cascades causing sex differences in disease. The number of X chromosomes, one vs. two, causes sex differences in models of metabolism and adiposity, of autoimmune disease, of Alzheimer’s disease, and bladder cancer. The underlying genes that cause the X chromosome effects are X-linked Kdm5c and Kdm6a, two lysine demethylases acting on H3K4 to activate or reduce gene expression elsewhere in the genome. The genes escape X inactivation and are expressed from all X chromosomes, so that XX cells express a higher dose than XY cells. This inherent inequality influences diverse tissues and diseases. Just as the discovery of gonadal hormonal sex-biasing factors, such as testosterone and estradiol, catalyzed waves of discovery of downstream mechanisms leading to sexual dimorphism in many tissues, we now expect the discovery of new sex chromosomal sex-biasing factors to lead to new research on novel pathways causing sex differences in diverse tissues related to numerous diseases.
Supported by NIH grants OD026560, HD100298, HD076125, DK083561, HL1311820
S3-4
A W-linked gene duplication underlies sexually dimorphic UV color vision in Heliconius butterflies
J.J. Emerson1,2, Mahul Chakraborty1, Russell Corbett-Detig3, Adriana Briscoe1
1Department of Ecology and Evolutionary Biology, University of California, Irvine
2Center for Systems Biology, University of California, Irvine
3Department of Biomolecular Engineering, University of California, Santa Cruz
In animals, color vision requires photoreceptor cells that are sensitive to different wavelengths of light. Unlike mammals, butterflies possess photoreceptor cells that are sensitive to the ultraviolet part of the spectrum due to the gene Ultraviolet-sensitive rhodopsin (UVRh). This gene has been duplicated in Heliconius butterflies. In individuals expressing both copies of UVRh, behavioral and electrophysiological studies demonstrate that these copies confer sensitivity between distinct wavelengths within the UV portion of the spectrum, enabling them to discriminate between those wavelengths. Interestingly, this phenotype is found only among females within a subset of Heliconius butterflies. However, the genetic mechanism behind this important sexually dimorphic phenotype remains a mystery. In order to determine the genetic basis of this trait, we used long reads and Hi-C scaffolding to build a reference-grade genome assembly of one of the butterflies with sexually dimorphic UV color vision, H. charithonia. We assemble each chromosome, including both sex chromosomes, into individual scaffolds, with most chromosomes spanning only one or a few contigs. We discovered that one copy of UVRh, UVRh1, is on the W chromosome, making it obligately female-specific. We use PCR assays to show that in species that exhibit sexually dimorphic UVRh1 expression, UVRh1 DNA is female-specific, whereas in species lacking dimorphism, UVRh1 DNA is found in both sexes, suggesting that UVRh1 attained W-linkage in one part of the clade, but maintained autosomal linkage elsewhere. We propose two evolutionary models explaining the acquisition of sexual dimorphism of UVRh1 in Heliconius and discuss how to distinguish in future work.
S3-5
G-quadruplexes Enriched on Drosophila Male X Chromosome Function as Insulators of Dosage Compensation Complex
Sheng Hu Qian1, Zhen-Xia Chen1
1Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
The evolution of sex chromosomes has resulted in X chromosome dosage in males half as much as in females. Dosage compensation or the two-fold upregulation in males was thus evolved to balance the gene expression between sexes. However, the step-wise evolutionary trajectory of dosage compensation during Y chromosome degeneration remains unclear.This study indicates that the specifically structured elements G-quadruplexes (G4s) are enriched on the X chromosome in Drosophila melanogaster. Meanwhile, on the X chromosome, the G4s are underrepresented in the H4K16 acetylated regions and the binding sites of dosage compensation complex male-specific lethal (MSL). Peaks of G4 density and potential are observed at the flanking regions of MSL binding sites, suggesting G4s act as insulators to precisely up-regulate certain regions in males. Thus, G4s may be involved in the evolution of dosage compensation process by fine-tuning one-dose proto-X chromosome regions around MSL binding sites during the gradual Y chromosome degeneration.
