Evolutionary analysis of functional divergence in TGF-? signaling pathway
TGF-? cytokines and their interacting receptors form an intricate signaling network and play important roles in cell differentiation and development. Members in gene families involved in this complicated pathway are usually conserved in sequence but distinct in temporal and tissue-specific expression. Starting from an evolutionary perspective, we have statistically tested the functional divergence in major pathway components, targeted the critical amino acid residues responsible for functional divergence. Our results show that altered functional constraints is a common pattern in the evolution of TGF-? pathway. Moreover, we have found the correlation between structural divergence and functional divergence in the extracellular ligand-binding domain of Type II receptors. This study helps understand the complex intrinsic mechanisms of signaling.
functional divergence tgf-? signaling pathway