Figure 4.

The Proposed Mechanism of Selection by Environmental Stresses on the Polymorphisms of p53 Codon 72 and MDM2 SNP309

The polymorphisms p53 codon 72 and MDM2 SNP309 are under selective pressure from the environmental stresses of winter temperature and UV radiation, respectively. The polymorphisms have an important impact upon the p53 pathway and help maintain efficient regulation under stressful conditions.

(A) In response to prolonged, cold temperatures, the p53 Arg72 allele is selected. This produces a more active form of p53, which increases the activation of genes such as LIF, SCO2, and TIGAR. p53 Arg72 may, therefore, be more efficient in regulating processes such as metabolism and embryo implantation, which would result in higher fitness levels.

(B) In contrast, the MDM2 SNP309 polymorphism is selected in areas with low UV radiation exposure. Migration of the Chinese populations northwards to areas with lower UV exposure would require less p53 in order to prevent any adverse effects of p53 hyperactivity, such as embryonic death. The MDM2 SNP309 G/G allele, which produces higher levels of Mdm2, is selected to counteract the high p53 levels, thereby conferring a selective advantage to these populations. This would prevent an overactive p53 pathway, while still enabling p53 to function as a tumor suppressor.