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Variable Gene Copy Number in Cancer-Related Pathways Is Associated With Cancer Prevalence Across Mammals.
Sophie Matthews1,2, Vahid Nikoonejad Fard3, Marc Tollis3,4
1School of Mathematical and Statistical Science, University of Galway, Galway, Ireland.
Molecular Biology and Evolution
|March 20, 2025
Summary
Mammals do not show a clear link between body size, lifespan, and cancer risk. Gene copy number variations, particularly in transforming growth factor beta pathways, may influence cancer rates across species.
Area of Science:
- Evolutionary Biology
- Genomics
- Cancer Research
Background:
- Cancer is a disease of multicellular organisms, yet mammals with larger bodies and longer lives don't show a higher cancer prevalence.
- Previous research suggested gene copy number might explain this, but only examined known cancer genes.
Purpose of the Study:
- To investigate the association between the copy number of all protein-coding genes and traits like longevity, body size, and cancer prevalence in mammals.
- To explore if aggregated gene copy number within biological pathways relates to these traits.
Main Methods:
- Phylogenetic generalized least squares analysis was used.
- Examined copy number of all protein-coding genes across 94 mammal species.
- Tested individual genes and sets of related genes for associations with longevity, body size, and cancer prevalence.
Main Results:
- No strong evidence was found that adaptive gene copy number changes explain the lack of correlation between cancer prevalence and body size or lifespan.
- Several biological processes showed associations between aggregate gene copy number and malignancy rate.
- The strongest association was observed for the gene set related to transforming growth factor beta.
Conclusions:
- Adaptive changes in gene copy number do not appear to be the primary driver for the observed cancer prevalence patterns in mammals.
- Gene copy number, especially within pathways like transforming growth factor beta, may contribute to variations in cancer rates across species.
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