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Updated: Jun 5, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Natural selection and functional genetic variation in the p53 pathway
Lara Sucheston1, David B Witonsky, Darcie Hastings
1Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14203, USA.
Human Molecular Genetics
|January 27, 2011
Summary
Global analysis of p53 pathway single-nucleotide polymorphisms (SNPs) suggests that TP53 Arg72Pro and MDM2 SNP309 are unlikely to be under selective pressure from climate variables. Population history is crucial for understanding selection signatures.
Area of Science:
- Human genetics
- Population genetics
- Evolutionary biology
Background:
- Allele frequencies of MDM2 SNP309 and TP53 Arg72Pro vary globally.
- Previous studies suggested climate-linked selection on these SNPs in East Asians.
- The role of neutral processes like human migration in these patterns was unclear.
Purpose of the Study:
- To investigate global correlations between TP53 Arg72Pro and MDM2 SNP309 allele frequencies and environmental variables.
- To assess if observed patterns are attributable to climate-driven selection versus neutral processes.
Main Methods:
- Genotyping of 971 individuals from 52 populations worldwide.
- Statistical analysis of SNP frequencies against latitude and climate variables.
- Controlling for neutral evolutionary processes.
Main Results:
- TP53 SNP showed a nominal association with winter short-wave radiation flux, but this was not significant after multiple testing correction.
- No significant correlation was found between the MDM2 SNP and any climate variable.
- Neither SNP exhibited a robust signal of selection driven by the tested climate variables.
Conclusions:
- The studied p53 pathway SNPs are unlikely to be under strong selective pressure from the investigated climate variables.
- Population history and neutral processes are essential considerations when evaluating signatures of natural selection.
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