Abstract
As one of the most conserved genes in vertebrates, FoxP2 is widely involved in a number of important physiological and developmental processes. We systematically studied the evolutionary history and functional adaptations of FoxP2 in teleosts. The duplicated FoxP2 genes (FoxP2a and FoxP2b), which were identified in teleosts using synteny and paralogon analysis on genome databases of eight organisms, were probably generated in the teleost-specific whole genome duplication event. A credible classification with FoxP2, FoxP2a and FoxP2b in phylogenetic reconstructions confirmed the teleost-specific FoxP2 duplication. The unavailability of FoxP2b in Danio rerio suggests that the gene was deleted through nonfunctionalization of the redundant copy after the Otocephala-Euteleostei split. Heterogeneity in evolutionary rates among clusters consisting of FoxP2 in Sarcopterygii (Cluster 1), FoxP2a in Teleostei (Cluster 2) and FoxP2b in Teleostei (Cluster 3), particularly between Clusters 2 and 3, reveals asymmetric functional divergence after the gene duplication. Hierarchical cluster analyses of hydrophobicity profiles demonstrated significant structural divergence among the three clusters with verification of subsequent stepwise discriminant analysis, in which FoxP2 of Leucoraja erinacea and Lepisosteus oculatus were classified into Cluster 1, whereas FoxP2b of Salmo salar was grouped into Cluster 2 rather than Cluster 3. The simulated thermodynamic stability variations of the forkhead box domain (monomer and homodimer) showed remarkable divergence in FoxP2, FoxP2a and FoxP2b clusters. Relaxed purifying selection and positive Darwinian selection probably were complementary driving forces for the accelerated evolution of FoxP2 in ray-finned fishes, especially for the adaptive evolution of FoxP2a and FoxP2b in teleosts subsequent to the teleost-specific gene duplication.
Highlights
FoxP2 is a key transcription factor gene in the FoxP subfamily [1]
Aside from its role in vocal communication, FoxP2 plays a pleiotropic role in cell differentiation, signal transduction, organogenesis, and neural circuit plasticity in the central nervous system (CNS) [3,4,5,6,9,10,11,12,13,14,15,16]
polymerase chain reaction (PCR) products were purified by Axyprep DNA Gel Extraction Kit (AxyGEN) and cloned into the pTA2 vector (Toyobo)
Summary
FoxP2 is a key transcription factor gene in the FoxP subfamily [1]. The gene possesses multiple functionally important domains, including the zinc-finger, leucine-zipper and forkhead box (Figure 1A). It has been found that Foxp plays a nonessential role in the production of innate emotional vocalizations in mouse pups [8]. Based on these findings, it is reasonable to infer that the role of FoxP2 in vocal communication is a derived function as opposed to an ancestral one. Aside from its role in vocal communication, FoxP2 plays a pleiotropic role in cell differentiation, signal transduction, organogenesis (e.g. lungs), and neural circuit plasticity in the central nervous system (CNS) [3,4,5,6,9,10,11,12,13,14,15,16]
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