Positive Selection on MMP3 Regulation Has Shaped Heart Disease Risk

摘要: Abstract Background: The evolutionary forces of mutation, natural selection, and genetic drift shape the pattern phenotypic variation in nature, but roles these defining distributions particular traits have been hard to disentangle. To better understand mechanisms contributing common humans, we investigated history a functional polymorphism upstream regulatory region MMP3 gene. This single base pair insertion/deletion variant, which results run either 5 or 6 thymidines 1608 bp from transcription start site, alters factor binding influences levels mRNA protein. contributes arterial risk coronary heart disease its progression. Results: Phylogenetic population analysis primate sequences indicate that site is rapidly evolving has hot spot for mutation tens millions years. We also find evidence action positive beginning approximately 24,000 years ago, increasing frequency high-expression allele Europe not elsewhere. Positive selection evident statistical tests differentiation among populations haplotype diversity within populations. Europeans greater elasticity suffer dramatically fewer events than they would had this occurred. Conclusions: Locally elevated rates strong on cis -regulatory variant shaped contemporary public health.