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.
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.
Hong
H
Shi
Si-jie
SJ
Tan
Hua
H
Zhong
Wenwei
W
Hu
Arnold
A
Levine
Chun-jie
CJ
Xiao
Yi
Y
Peng
Xue-bin
XB
Qi
Wei-hua
WH
Shou
Run-lin Z
RL
Ma
Yi
Y
Li
Bing
B
Su
Xin
X
Lu
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