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The tumor suppressor p53 is a master sensor of stress. Two human-specific polymorphisms, p53 codon 72 and MDM2 SNP309, influence the activities of p53. There is a tight association between cold winter temperature and p53 Arg72 and between low UV intensity and MDM2 SNP309 G/G in a cohort of 4029 individuals across Eastern Asia that suggests causative selection. Moreover, the two polymorphisms are not coselected. Haplotype-based selection analysis further suggests that this is a striking example of two functional polymorphisms being strongly selected for in human populations in response to environmental stresses.

Original publication




Journal article


Am J Hum Genet

Publication Date





534 - 541


Alleles, Asian Continental Ancestry Group, Base Sequence, Cohort Studies, Cold Climate, DNA Primers, Ethnic Groups, Far East, Gene Frequency, Genes, p53, Haplotypes, Humans, Leukemia Inhibitory Factor, Models, Genetic, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-mdm2, Seasons, Selection, Genetic, Stress, Physiological, Temperature, Transcriptional Activation, Ultraviolet Rays