Human Adaptive Evolution at Myostatin (GDF8), a Regulator of Muscle Growth

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Am J Hum Genet. 2006 Dec;79(6):1089-97.

Human Adaptive Evolution at Myostatin (GDF8), a Regulator of Muscle

Growth.

Saunders MA, Good JM, Lawrence EC, Ferrell RE, Li WH, Nachman MW.

Department of Ecology and Evolution, University of Chicago, Chicago,

IL, 60637, USA.

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.