Human Single-Cell RNA-Sequencing Data Supports the Hypothesis of X Chromosome Insensitivity but Is Ineffective in Testing the Dosage Compensation Model.

ABSTRACT: A controversy in evolutionary genetics is whether active dosage compensation is necessary to resolve the gene dosage imbalance between the X chromosome and autosomes. ScRNA-seq data could provide insight into this issue. However, it's crucial to carefully evaluate whether inherent characteristics of scRNA-seq, such as the sparsity of detected genes, might bias the X:AA expression ratio in mammals. This study evaluated two common strategies for selecting genes in the calculation of X:AA, namely, filter-by-expression and filter-by-fraction, with simulated scRNA-seq and bulk RNA-seq datasets. We found that both strategies produce an inflated X:AA, thus artifactually supporting dosage compensation. Analyzing empirical human Smart-seq2 data, results from the filter-by-expression strategy sugges

SUBMITTER: Chen J 

PROVIDER: S-EPMC11811734 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature