bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.10.24.620066

Regulation of Sex-biased Gene Expression by the Ancestral X-Y Chromosomal Gene Pair Kdm5c-Kdm5d

Malcore, R. M.·Samanta, M. K.·Kalantry, S.·Iwase, S.
View original source ↗Export metadata ↓

Abstract

Conventionally, Y-linked Sry is thought to drive sex differences by triggering differential hormone production. Ancestral X-Y gene pairs, however, are hypothesized to drive hormone-independent sex differences. Here, we show that the X-Y gene pair Kdm5c-Kdm5d regulates sex-biased gene expression in pluripotent mouse embryonic stem cells (ESCs). Wild-type (WT) XX female ESCs exhibit >2-fold higher expression of 409 genes relative to WT XY male ESCs. Conversely, WT XY male ESCs exhibit >2-fold higher expression of 126 genes compared to WT XX female ESCs. Loss of Kdm5c in female ESCs downregulates female-biased genes. In contrast, loss of either Kdm5c or Kdm5d in male ESCs upregulates female-biased genes and downregulates male-biased genes, effectively neutralizing sex-biased gene expression. KDM5C promotes the expression of Kdm5d and several other Y-linked genes in male ESCs. Moreover, ectopic Kdm5d expression in female ESCs is sufficient to drive male-biased gene expression. These results establish Kdm5c-Kdm5d as critical regulators of sex-biased gene expression.

Explore related subjects

geneticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Malcore, R. M., Samanta, M. K., Kalantry, S., Iwase, S.. 2024-10-27. Regulation of Sex-biased Gene Expression by the Ancestral X-Y Chromosomal Gene Pair Kdm5c-Kdm5d. https://doi.org/10.1101/2024.10.24.620066

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Generation of a transgenic cephalopod

Coleoid cephalopods (cuttlefish, octopus, and squid) are marine mollusks with elaborate nervous systems that support a diverse repertoire of complex behaviors. These include the neural control of the color, pattern, and texture of the skin, facilitating both adaptive camouflage and innate patterning that may reflect internal state. The development of transgenic cephalopods expressing fluorescent proteins, optogenetic actuators, and reporters of neural activity would contribute a new and important technology to cephalopod biology. The generation of transgenic cephalopods, however, has remained a major challenge. Here, we report the development of stable transgenic dwarf cuttlefish (Ascarosepion bandense) expressing ubiquitous nuclear-localized mScarlet, a red fluorescent protein. We evaluated multiple strategies for transgenesis, and established cuttlefish lines using both CRISPR and the transposons Sleeping Beauty and Minos. The stable expression of transgenes enabled live imaging of cell dynamics during embryonic development. The Minos transposon emerged as the most efficient transgenesis strategy and is adaptable to promoters and transgenes of choice. These strategies now enable the generation of diverse genetic tools for mechanistic studies of cephalopod biology.

genetics↗
bioRxiv2026

Large language model-based bibliometric evaluation of population descriptors in human genetics

As the use of population descriptors such as race, ethnicity, and ancestry have become increasingly common in modern genetics research, there have been growing calls to critically examine their use. Most notably, in 2023, the National Academies of Science, Engineering, and Medicine (NASEM) published a report titled Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field, which included eight specific and actionable recommendations for researchers to implement the ethical and accurate use of population descriptors in genetic research. Here, we use the 2023 NASEM report as a benchmark to analyze the use of population descriptors in genome-wide association studies (GWAS). We develop a general toolkit for large language model-based bibliometrics, operationalize the report's recommendations into an evaluation framework, and apply this framework to evaluate all 4,007 papers from the GWAS Catalog published between 2007 and 2025 with full text available on PubMedCentral. We find significant improvements in adherence to NASEM report recommendations over time. However, most improvements predate the publication of the NASEM report itself, suggesting the report functioned primarily as a synthesis of existing best practices rather than a catalyst for change. We conclude by highlighting opportunities for growth in the field of human genetics.

genetics↗
bioRxiv2026

Mitigating biases of rescaling in forward-in-time population genetic simulations

Forward-in-time population genetic simulations are widely used in evolutionary analyses, but simulating large populations and long genomic regions remains computationally demanding. To reduce this cost, parameter rescaling is widely employed, in which the original evolutionary process is approximated by one with a smaller population size and fewer generations. Recently, several studies using the SLiM simulator have raised concerns about the accuracy of this rescaling approach. In this study, we show that many of the biases reported in these studies can be mitigated by using a different simulation algorithm. These results reveal that the accuracy of parameter rescaling depends on how well the simulation algorithm preserves diffusion-limit properties under rescaling.

genetics↗