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A Bioinformatics Pipeline for Investigating Molecular Evolution and Gene Expression using RNA-seq
Published on: May 28, 2021
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Systemic evolutionary changes in mammalian gene expression.
Alexander E Vinogradov1, Olga V Anatskaya1
1Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
Bio Systems
|September 25, 2020
Summary
Evolutionary gene expression changes are systemic, occurring in the same direction across mammalian tissues. These unidirectionally changed genes (UCGs) are linked to fundamental biological processes and diseases, offering insights into longevity and health variations.
Area of Science:
- Evolutionary biology
- Genomics
- Systems biology
Background:
- Gene expression changes are crucial for evolution and evolutionary medicine.
- Understanding systemic changes in gene expression across tissues is vital.
Purpose of the Study:
- To investigate the relationship between the statistical significance of evolutionary gene expression changes and their unidirectionality across mammalian tissues.
- To identify pathways enriched in unidirectionally changed genes (UCGs) and their functional implications.
Main Methods:
- Comparative analysis of orthologous gene expression across five or six homologous mammalian tissues.
- Statistical assessment of gene expression changes and their directionality (upward/downward).
- Enrichment analysis of UCGs in biological pathways and disease associations.
Main Results:
- A strong correlation exists between statistically significant evolutionary gene expression changes and across-tissue unidirectionality.
- Over 90% of highly significant changes were unidirectional, indicating systemic, whole-organism level alterations.
- UCGs are enriched in housekeeping genes and pathways related to gene expression, cell cycle, apoptosis, and neurodegenerative diseases (Parkinson's, Alzheimer's, Huntington's).
Conclusions:
- Pronounced evolutionary gene expression changes in mammals are systemic and functional, not neutral.
- Systemic changes likely maintain physiological balance across tissues during evolution.
- Findings provide insights into variations in longevity, cancer susceptibility, and neurodegenerative diseases, and can guide cis-regulatory code studies.
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