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Updated: Sep 6, 2025
10:06
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
7.8K
Tissue Specificity of Gene Expression Evolves Across Mammal Species
1Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, California, USA.
Summary
Gene expression tissue specificity is largely conserved across species, but 380 genes are shifting. These shifting genes, and cassette exons, show lower conservation, impacting disease model validity.
Area of Science:
- Genomics
- Evolutionary Biology
- Transcriptomics
Background:
- Tissue-specific gene expression is crucial for understanding hereditary diseases and validating animal models.
- Evolutionary analysis of tissue specificity offers insights into gene function and conservation.
- Advancements in sequencing technology enable large-scale cross-species transcriptomic studies.
Purpose of the Study:
- To investigate the conservation and evolution of tissue specificity in gene expression across multiple species.
- To identify genes and regulatory elements that have shifted their tissue specificity during evolution.
- To assess the relationship between evolutionary conservation and tissue-specificity shifts.
Main Methods:
- Comparative analysis of transcriptomic data from humans, cynomolgus macaques, rats, mice, and dogs.
- Examination of gene expression patterns across 13 different tissues for each species.
- Analysis of gene conservation at the third codon position and synonymous codon usage bias.
- Comparison of tissue specificity shifts between protein-coding genes and cassette exons.
Main Results:
- Homologous gene expression tissue specificity is generally conserved across the studied species.
- A total of 380 genes exhibit shifts or ongoing shifts in tissue specificity.
- Genes with shifting tissue specificity are less conserved evolutionarily than those with stable specificity or housekeeping genes.
- Tissue-specificity-shifting genes show reduced conservation at the third codon position, suggesting relaxed codon usage bias.
- Cassette exons are more prone to shifting tissue specificity in splicing compared to entire genes.
Conclusions:
- While gene expression tissue specificity is largely conserved, significant evolutionary shifts occur in a subset of genes and splicing elements.
- The reduced conservation of shifting genes and exons may reflect adaptation to new tissue-specific functions or relaxed evolutionary constraints.
- Understanding these shifts is vital for interpreting gene function, disease mechanisms, and the relevance of animal models in biomedical research.
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