Winter temperature and UV are tightly linked to genetic changes in the p53 tumor suppressor pathway in Eastern Asia.
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.
Shi
Hong
H
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology and Kunming Primate Research Centre, Chinese Academy of Sciences, Kunming 650223, PR China.
Tan
Si-jie
SJ
Zhong
Hua
H
Hu
Wenwei
W
Levine
Arnold
A
Xiao
Chun-jie
CJ
Peng
Yi
Y
Qi
Xue-bin
XB
Shou
Wei-hua
WH
Ma
Run-lin Z
RL
Li
Yi
Y
Su
Bing
B
Lu
Xin
X
D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015331:Cohort Studies; D003081:Cold Climate / Q000009:adverse effects*; D017931:DNA Primers / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005202:Asia, Eastern; D005787:Gene Frequency; D016158:Genes, p53 / Q000528:radiation effects*; D006239:Haplotypes; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000235:genetics; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D012621:Seasons; D012641:Selection, Genetic; D013312:Stress, Physiological / Q000528:radiation effects; D013696:Temperature; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
D017931:DNA Primers; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2