Evolution of myostatin in vertebrates: Is there evidence for positive selection?

Abstract

The transforming growth factor (TGF) superfamily includes signaling polypeptides that are responsible for regulating a variety of cellular functions that aVect embryo development and tissue homeostasis (Herpin et al., 2004). Myostatin, also known as growth and diVerentiation factor-8 (GDF-8), is a member of the TGFsuperfamily that has received considerable attention in the past few years due to its role as a negative regulator of vertebrate muscle growth (McPherron et al., 1997; Grobet et al., 1997, 1998; Kambadur et al., 1997; Radaelli et al., 2003). The myostatin mechanism for controlling muscle growth seems to be based on the inhibition of myoblast proliferation by stimulating cell cycle withdrawal while simultaneously inhibiting diVerentiation and inducing cellular quiescence (Thomas et al., 2000). The predicted human, rat, mouse, porcine, chicken, and turkey myostatin proteins are identical in the biologically active carboxy-terminal region, suggesting that this gene is highly conserved throughout vertebrate evolution (McPherron and Lee, 1997). Given its key role in the regulation of muscle mass deposition during embryogenesis, one could expect that myostatin would be subject to strong purifying selection to allow skeletal muscles to achieve their ideal size in the body of vertebrate organisms. However, recent studies have presented evidence of positive selection on myostatin, particularly in artiodactylid mammals and teleost Wsh (Limberles et al., 2001; Tellgren et al., 2004). In proteincoding genes, positive selection might be detected by computing the ratio between the rate of nonsynonymous (amino acid altering) nucleotide substitutions per nonsyn-