Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Asia, Eastern
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Asian People / genetics
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Base Sequence
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Cohort Studies
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Cold Climate / adverse effects*
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DNA Primers / genetics
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Ethnicity / genetics
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Gene Frequency
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Genes, p53 / radiation effects*
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Haplotypes
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Humans
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Leukemia Inhibitory Factor / genetics
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Models, Genetic
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Polymorphism, Single Nucleotide
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Proto-Oncogene Proteins c-mdm2 / genetics
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Seasons
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Selection, Genetic
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Stress, Physiological / radiation effects
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Temperature
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Transcriptional Activation
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Ultraviolet Rays*
Substances
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DNA Primers
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LIF protein, human
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Leukemia Inhibitory Factor
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2