Sex-biased gene expression across mammalian organ development and evolution

Science, Год журнала: 2023, Номер 382(6670)

Опубликована: Ноя. 2, 2023

Sexually dimorphic traits are common among mammals and specified during development through the deployment of sex-specific genetic programs. Because little is known about these programs, we investigated them using a resource gene expression profiles in males females throughout five organs (human, mouse, rat, rabbit, opossum) bird (chicken). We found that sex-biased varied considerably across species was often cell-type specific. Sex differences increased abruptly around sexual maturity instead increasing gradually organ development. Finally, evolved rapidly at level, with between evolutionary mechanisms used, but more slowly cellular same cell types being sexually species.

Язык: Английский

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Sex disparities in mortality and cardiovascular outcomes in chronic kidney disease

Clinical Kidney Journal, Год журнала: 2024, Номер 17(3)

Опубликована: Фев. 20, 2024

ABSTRACT Sex (biologically determined) and gender (socially constructed) modulate manifestations prognosis of a vast number diseases, including cardiovascular disease (CVD) chronic kidney (CKD). CVD remains the leading cause death in CKD patients. Population-based studies indicate that women present higher prevalence experience less than men all stages, although this is not as clear patients on dialysis or transplantation. When compared to general population same sex, has more negative impact replacement therapy. European recipients transplants have life expectancy up 44.8 19.8 years lower, respectively, their counterparts similar age population. For men, these figures stand at 37.1 16.5 years, representing 21% 20% difference, respectively. Hormonal, genetic, societal, cultural influences may contribute sex-based disparities. To gain comprehensive understanding differences implications for patient care, well-designed clinical trials involve larger representation focus sex-related variables are urgently needed. This narrative review emphasizes importance acknowledging epidemiology sex disparities among Such insights can guide research into underlying pathophysiological mechanisms, optimized treatment strategies ultimately, improved outcomes.

Язык: Английский

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Evolution of chemosensory tissues and cells across ecologically diverse Drosophilids

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 5, 2024

Abstract Chemosensory tissues exhibit significant between-species variability, yet the evolution of gene expression and cell types underlying this diversity remain poorly understood. To address these questions, we conducted transcriptomic analyses five chemosensory from six Drosophila species integrated findings with single-cell datasets. While stabilizing selection predominantly shapes transcriptomes, thousands genes in each tissue have evolved differences. Genes that changed one often multiple other but at different past epochs are more likely to be type-specific than unchanged genes. Notably, chemosensory-related undergone widespread changes, numerous species-specific gains/losses including novel chemoreceptors patterns. Sex differences also pervasive, a D. melanogaster- specific excess male-biased sensory muscle cells its forelegs. Together, our provide new insights for understanding evolutionary changes both global individual levels.

Язык: Английский

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A male-essential microRNA is key for avian sex chromosome dosage compensation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 7, 2024

Birds have a sex chromosome system in which females are heterogametic (ZW) and males homogametic (ZZ). The differentiation of avian chromosomes from ancestral autosomes entailed the loss most genes W during evolution. However, to what extent mechanisms evolved that counterbalance consequences this extensive gene dosage reduction female birds has remained unclear. Here we report functional vivo evolutionary analyses Z-chromosome-linked microRNA (miR-2954) with strongly male-biased expression was previously proposed play key role compensation 1 . We knocked out miR-2954 chicken, resulted early embryonic lethality homozygous knockout males, likely due highly specific upregulation dosage-sensitive Z-linked target miR-2954. Our further revealed these become upregulated on single Z Altogether, our work unveils scenario where pressures following led evolution transcriptional not only but also male birds. resulting overabundance transcripts combined activity two copies turn offset by emergence targeted miR-2954-mediated transcript degradation mechanism findings demonstrate unique essential for survival.

Язык: Английский

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Evolution of translational control and the emergence of genes and open reading frames in human and non-human primate hearts

Nature Cardiovascular Research, Год журнала: 2024, Номер 3(10), С. 1217 - 1235

Опубликована: Сен. 24, 2024

Evolutionary innovations can be driven by changes in the rates of RNA translation and emergence new genes small open reading frames (sORFs). In this study, we characterized transcriptional translational landscape hearts four primate two rodent species through integrative ribosome transcriptomic profiling, including adult left ventricle tissues induced pluripotent stem cell-derived cardiomyocyte cell cultures. We show here that efficiencies subunits mitochondrial oxidative phosphorylation chain complexes IV V evolved rapidly across mammalian evolution. Moreover, discovered hundreds species-specific lineage-specific genomic emerged during evolution heart, 551 genes, 504 sORFs 76 evolutionarily conserved displaying human-specific cardiac-enriched expression. Overall, our work describes evolutionary processes mechanisms have shaped cardiac transcription recent sheds light on how these contribute to development disease.

Язык: Английский

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A panoramic view of cell population dynamics in mammalian aging

Science, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

To elucidate aging-associated cellular population dynamics, we present PanSci , a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissues across different life stages, sexes, and genotypes. This comprehensive dataset reveals more than 3,000 unique states 200 cell populations. Our panoramic analysis uncovered organ-, lineage-, sex-specific shifts of dynamics during lifespan progression. Moreover, identify both systematic organ-specific alterations in immune populations associated with aging. We further explored the regulatory roles system on aging pinpointed specific age-related expansions that are lymphocyte dependent. “cell-omics” strategy enhances comprehension lays groundwork for exploring complex networks diseases.

Язык: Английский

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Sex-biased gene expression across tissues reveals unexpected differentiation in the gills of the threespine stickleback

Peer Community Journal, Год журнала: 2025, Номер 5

Опубликована: Янв. 13, 2025

Sexual dimorphism can evolve through sex-specific regulation of the same gene set. However, sex chromosomes also facilitate this by directly linking expression to sex. Moreover, differences in content between heteromorphic contribute sexual dimorphism. Understanding patterns sex-biased across organisms is important for gaining insight into evolution and chromosomes. studying species with recently established help understand evolutionary dynamics loss dosage compensation. The three-spined stickleback known its strong dimorphism, especially during reproductive period. Sex determined a young XY chromosome pair non-recombining region divided three strata, which have started degenerate. Using high multiplexing capability 3′ QuantSeq sequence transcriptome liver, gills, brain, we provide first characterization transcriptomes from ~80 sticklebacks (40 males 40 females) collected natural population We find that liver extremely differentiated sexes (36% autosomal genes) reflects ongoing reproduction, while brain shows very low levels differentiation (0.78%) no functional enrichment. Finally, gills exhibit (5%), suggesting should be considered physiological ecotoxicological studies gill responses fishes. hemizygous genes mainly driven lack conserved copies on both likely degeneration Y allele down-regulation male-beneficial mutations X chromosome.

Язык: Английский

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Evolutionary divergence between homologous X–Y chromosome genes shapes sex-biased biology

Nature Ecology & Evolution, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Язык: Английский

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Genetic and Pharmacological Inhibition of Metabotropic Glutamate Receptor Signalling Extends Lifespan in Drosophila

Aging Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Invertebrate models have been instrumental in advancing our understanding of the molecular mechanisms ageing. The isolation single gene mutations that both extend lifespan and improve age-related health identified potential targets for therapeutic intervention to alleviate morbidity. Here, we find genetic loss function G protein-coupled metabotropic glutamate receptor (DmGluRA) Drosophila extends female flies. This longevity phenotype was accompanied by lower basal levels oxidative stress improved tolerance, differences early-life behavioural markers. Gene expression changes DmGluRA mutants reduced ribosome biogenesis, a hallmark longevity, as key process altered these animals. We further show pro-longevity effects signalling are dependent on fly homologue Fragile X Mental Retardation Protein (FMRP), an important regulator ribosomal protein translation. Importantly, can recapitulate extension using specific pharmacological inhibitor mGluR activity. Hence, study identifies receptors therapeutics.

Язык: Английский

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Sex Chromosomes and Sex Hormones: Dissecting the Forces That Differentiate Female and Male Hearts

Circulation, Год журнала: 2025, Номер 151(7), С. 474 - 489

Опубликована: Фев. 17, 2025

The heart is a highly sex-biased organ, as sex shapes innumerable aspects of health and disease. Sex chromosomes hormones —testosterone, progesterone, estrogen— establish perpetuate the division between male female myocardium. Of these differentiating factors, insulating effects estrogen have been rigorously interrogated reviewed, whereas influence chromosomes, testosterone, progesterone remains in dispute or ill-defined. Here, we synthesize growing evidence that substantially bias form, function, dysfunction context-dependent fashion. discrete protective functions ascribed to each 3 receptors are also enumerated. Subsequently, overview obstacles historically discouraged inclusion subjects basic science such impact estrus cycle reproductive senescence on data reliability reproducibility. Furthermore, weigh utility several common strategies intercept rescue sex-specific protection. Last, warn compounds animal chow cell culture interfere with signaling. In sum, survey controversies challenges stem from sex-inclusive cardiovascular research, comparing possible causes cardiac bias, elucidating chromosome hormone-dependent processes heart, describing lapses imperil work, illuminating facets yet unexplored still uncertain.

Язык: Английский

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