Evidence for positive selection on the Osteogenin (BMP3) gene in human populations.
BACKGROUND
Human skeletal system has evolved rapidly since the dispersal of modern humans from Africa, potentially driven by selection and adaptation. Osteogenin (BMP3) plays an important role in skeletal development and bone osteogenesis as an antagonist of the osteogenic bone morphogenetic proteins, and negatively regulates bone mineral density.


RESULTS
Here, we resequenced the BMP3 gene from individuals in four geographically separated modern human populations. Features supportive of positive selection in the BMP3 gene were found including the presence of an excess of nonsynonymous mutations in modern humans, and a significantly lower genetic diversity that deviates from neutrality. The prevalent haplotypes of the first exon region in Europeans demonstrated features of long-range haplotype homogeneity. In contrast with findings in European, the derived allele SNP Arg192Gln shows higher extended haplotype homozygosity in East Asian. The worldwide allele frequency distribution of SNP shows not only a high-derived allele frequency in Asians, but also in Americans, which is suggestive of functional adaptation.


CONCLUSIONS
In conclusion, we provide evidence for recent positive selection operating upon a crucial gene in skeletal development, which may provide new insight into the evolution of the skeletal system and bone development.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Dong-Dong
DD
Wu
Wei
W
Jin
Xiao-Dan
XD
Hao
Nelson Leung Sang
NL
Tang
Ya-Ping
YP
Zhang
D005075:Biological Evolution; D001846:Bone Development / Q000235:genetics; D055398:Bone Morphogenetic Protein 3 / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
D055398:Bone Morphogenetic Protein 3