Human adaptive evolution at Myostatin (GDF8), a regulator of muscle growth

Am J Hum Genet. 2006 Dec;79(6):1089-97. doi: 10.1086/509707. Epub 2006 Oct 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • African Continental Ancestry Group / genetics
  • Animals
  • European Continental Ancestry Group / genetics
  • Evolution, Molecular*
  • Gene Frequency
  • Genetic Variation
  • Haplotypes / genetics
  • Humans
  • Mammals / genetics
  • Muscle Development / physiology*
  • Myostatin
  • Polymorphism, Single Nucleotide
  • Selection, Genetic
  • Transforming Growth Factor beta / physiology*


  • MSTN protein, human
  • Mstn protein, mouse
  • Myostatin
  • Transforming Growth Factor beta