Comparative Transcriptomics Suggests that Breast Secretory Epithelium Reuses Gene Repertoires Conserved Across...

Area of Science:

• Molecular evolutionary biology
• Genomics
• Developmental biology

Background:

• Complex traits often evolve by repurposing existing molecular components rather than through novel gene emergence.
• Understanding how pre-existing gene repertoires are reorganized for tissue-specific functions is crucial for molecular evolutionary studies.

Purpose of the Study:

• To investigate the molecular evolutionary organization of gene expression programs in human breast tissue.
• To compare breast tissue transcriptomes with other secretory epithelial tissues across vertebrates.
• To determine if breast tissue specialization relies on novel genes or conserved gene redeployment.

Main Methods:

• Utilized bulk RNA-sequencing (RNA-seq) data from the Genotype-Tissue Expression (GTEx) project.
• Performed co-expression network analysis and single-cell reference integration.
• Conducted cross-vertebrate orthology assessment to identify conserved genes and modules.

Main Results:

• Identified gene expression modules broadly shared across epithelial secretory tissues, enriched in breast tissue, or specific to female breast samples.
• Demonstrated that genes enriched in breast tissue are largely evolutionarily conserved across vertebrates.
• Found partial overlap in co-expression modules between breast and other secretory epithelial tissues, particularly in secretion, vesicle trafficking, and extracellular matrix pathways.

Conclusions:

• Human breast secretory epithelium achieves specialization by integrating conserved vertebrate gene repertoires.
• Tissue specialization is driven by the regulatory redeployment of existing, evolutionarily conserved genes, not by the extensive emergence of mammal-specific genes.