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Abstract:
Dramatic skeletal changes have evolved within most vertebrate groups. High-resolution mapping experiments with natural populations of sticklebacks identify two distinct, but very closely linked loci that regulate different aspects of armour plate size. The Growth/differentiation factor 6 (GDF6), a secreted bone morphogenetic protein, is the only gene in both intervals. Freshwater fish with reduced armour plates show elevated levels of GDF6 expression and transgenic overexpression of GDF6 in large-plated marine fish results in smaller or missing plates. Gdf6 null mice have skeletal phenotypes, and in humans there is a unique loss of conserved non-coding element in the GDF6 gene. The chimpanzee allele of the enhancer missing in humans drives expression in the hindlimbs but not forelimbs, in anatomic domains that have been specifically modified during the human transition to bipedalism. These results suggest that both upregulation and downregulation of GDF6 contribute to natural variation in skeletal morphology in fish and primates.
