Abstract
GDF5 is a member of the bone morphogenetic protein (BMP) gene family, and plays an important role in the development of the skeletal system. Variants of the gene are associated with osteoarthritis and height in some human populations. Here, we resequenced the gene in individuals from four geographically separated human populations, and found that the evolution of the promoter region deviated from neutral expectations, with the sequence evolution driven by positive selection in the East Asian population, especially the haplotypes carrying the derived alleles of 5′ UTR SNPs rs143384 and rs143383. The derived alleles of rs143384 and rs143383, which are associated with a risk of osteoarthritis and decreased height, have high frequencies in non-Africans and show strong extended haplotype homozygosity and high population differentiation in East Asian. It is concluded that positive selection has driven the rapid evolution of the two osteoarthritis osteoarthritis-risk and decreased height associated variants of the human GDF5 gene, and supports the suggestion that the reduction in body size during the terminal Pleistocene and Holocene period might have been an adaptive process influenced by genetic factors.
Highlights
Humans are characterized by many unique traits, such as cognitive ability, language speaking, special skeletal anatomy, and susceptibility to diseases, which distinguish us from our closest relative, the chimpanzee
The observations for the exon 2 data support the hypothesis that positive selection, and not demographic history, operated on the 59 UTR region, as demographic history should influence all parts of the gene and would be expected to produce the same pattern of polymorphisms in both the exons 1 and 2 regions
Our previous study indicated that positive selection operated on skeletal genes in non-African populations, including Europeans and East Asians [4]
Summary
Humans are characterized by many unique traits, such as cognitive ability, language speaking, special skeletal anatomy, and susceptibility to diseases, which distinguish us from our closest relative, the chimpanzee (reviewed in [1]). Many studies have examined the genetic bases of the evolutionary patterns of these phenotypes and have identified the role of positive selection on genes in processes such as brain development in the human lineage and skin pigmentation among modern human populations (reviewed in [2,3]). The allele A of the SNP rs143383 in the 59 promoter region of the GDF5 gene was found to be associated with an increased risk of osteoarthritis, and shows decreased transcriptional activity of GDF5 in chondrogenic cells [13,14,15] This allele is associated with decreased height, which may be due to the lower expression of GDF5 that could lead to a reduction in limb bone growth [16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
