Abstract
The functional divergence of transcriptional factors is critical in the evolution of transcriptional regulation. However, the mechanism of functional divergence among these factors remains unclear. Here, we performed an evolutionary analysis for positive selection in members of the myogenic regulatory factor (MRF) gene family of vertebrates. We selected 153 complete vertebrate MRF nucleotide sequences from our analyses, which revealed substantial evidence of positive selection. Here, we show that sites under positive selection were more frequently detected and identified from the genes encoding the myogenic differentiation factors (MyoG and Myf6) than the genes encoding myogenic determination factors (Myf5 and MyoD). Additionally, the functional divergence within the myogenic determination factors or differentiation factors was also under positive selection pressure. The positive selection sites were more frequently detected from MyoG and MyoD than Myf6 and Myf5, respectively. Amino acid residues under positive selection were identified mainly in their transcription activation domains and on the surface of protein three-dimensional structures. These data suggest that the functional gain and divergence of myogenic regulatory factors were driven by distinct positive selection of their transcription activation domains, whereas the function of the DNA binding domains was conserved in evolution. Our study evaluated the mechanism of functional divergence of the transcriptional regulation factors within a family, whereby the functions of their transcription activation domains diverged under positive selection during evolution.
Highlights
Recent studies in evolutionary genetics have provided several lines of evidence supporting the role of positive selection in the evolution of many genes
The third MYF5 domain was only conserved in the myogenic determination factors (Myf5 and myogenic differentiation 1 (MyoD)), but not in the myogenic differentiation factors (Myf6 and MyoG) (Fig. 1A)
In this study we investigated the evolution of the four myogenic regulatory factor (MRF) genes in order to determine the role of positive selection in the functional divergence of this transcription factor family
Summary
Recent studies in evolutionary genetics have provided several lines of evidence supporting the role of positive selection in the evolution of many genes. We performed an evolutionary analysis to study the role of positive selection in the evolution of myogenic regulatory factors (MRFs), which comprise the transcription factor family that regulates myogenesis. The myogenic regulatory factors (MRFs) play key roles in myoblast determination and differentiation [5,6]. The MRF family includes myogenic differentiation 1 (MyoD), myogenic factor 5 (Myf5), myogenin (MyoG), and Myf (MRF4) genes. MyoG and Myf are myogenic differentiation factors that contribute to the differentiation of myoblasts and act downstream of Myf and MyoD, though Myf partly acts at both the determination and differentiation levels [6,9,10]. Myf and MyoD have redundant functions in myoblast determination and can compensate for the functional loss of each other, Myf plays a more critical role during the early determination of epaxial muscle, whereas MyoD is more critical for hypaxial muscle determination [8,11]
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