GDF-8 (Myostatin) 1mg

1 vial GDF-8 (Myostatin) 1mg

GDF-8 (Myostatin) 1mg

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Myostatin (GDF8) is a negative regulator of muscle growth in mammals, and loss-of-function mutations are associated with increased skeletal-muscle mass in mice, cattle, and humans. Here, we show that positive natural selection has acted on human nucleotide variation at GDF8, since the observed ratio of nonsynonymous:synonymous changes among humans is significantly greater than expected under the neutral model and is strikingly different from patterns observed across mammalian orders. Furthermore, extended haplotypes around GDF8 suggest that two amino acid variants have been subject to recent positive selection. Both mutations are rare among non-Africans yet are at frequencies of up to 31% in sub-Saharan Africans. These signatures of selection at the molecular level suggest that human variation at GDF8 is associated with functional differences.
The genetic basis of muscle development and growth has been extensively studied in an effort to treat myopathies1 and to understand individual variation in athletic performance.2 Because musculature features might have provided a fitness advantage during human evolution, candidate genes related to musculature may have been targets of natural selection in humans.
The myostatin gene, also called “growth and differentiation factor 8” (GDF8 [MIM 601788]) encodes a negative regulator of skeletal-muscle growth.3 First described in the mouse, myostatin is expressed in different muscles throughout the body, both during early development and in adults. Mouse null mutants are significantly larger than wild-type animals, with 200%–300% more skeletal-muscle mass because of an increase in the number of myocytes (hyperplasy) and an increase in the size of muscle fibers (hypertrophy).3 A similar phenotype is seen in some breeds of double-muscled cattle that also have myostatin mutations.4,5 A loss-of-function mutation in the myostatin gene (a missplicing change in IVS1:G378A) has been associated with muscle hypertrophy in a human subject,6 and myostatin expression levels have been shown to be inversely correlated with muscle mass in healthy and HIV-infected subjects.7 These data suggest that myostatin acts in a similar fashion among all mammals. Here, we tested the hypothesis that patterns of human nucleotide variation at GDF8 have been shaped by positive natural selection.

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GDF-8 (Myostatin) 1mg

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