Sex-biased gene expression at single-cell resolution: cause and consequence of sexual dimorphism
Bibliographic record
Abstract
Gene expression differences between males and females are thought to be key for the evolution of sexual dimorphism, and sex-biased genes are often used to study the molecular footprint of sex-specific selection. However, gene expression is often measured from complex aggregations of diverse cell types, making it difficult to distinguish between sex differences in expression that are due to regulatory rewiring within similar cell types and those that are simply a consequence of developmental differences in cell-type abundance. To determine the role of regulatory versus developmental differences underlying sex-biased gene expression, we use single-cell transcriptomic data from multiple somatic and reproductive tissues of male and female guppies, a species that exhibits extensive phenotypic sexual dimorphism. Our analysis of gene expression at single-cell resolution demonstrates that nonisometric scaling between the cell populations within each tissue and heterogeneity in cell-type abundance between the sexes can influence inferred patterns of sex-biased gene expression by increasing both the false-positive and false-negative rates. Moreover, we show that, at the bulk level, the subset of sex-biased genes that are the product of sex differences in cell-type abundance can significantly confound patterns of coding-sequence evolution. Taken together, our results offer a unique insight into the effects of allometry and cellular heterogeneity on perceived patterns of sex-biased gene expression and highlight the power of single-cell RNA-sequencing in distinguishing between sex-biased genes that are the result of regulatory change and those that stem from sex differences in cell-type abundance, and hence are a consequence rather than a cause of sexual dimorphism.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".