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

Matthew A. Saunders, Jeffrey M. Good, Elizabeth C. Lawrence, Robert E. Ferrell, Wen Hsiung Li, Michael W. Nachman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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.

Original languageEnglish
Pages (from-to)1089-1097
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - Dec 2006


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