Mutational, functional and evolutionary analysis of interleukin-11 in Homo sapiens: A detailed in silico exploration for platelet recovery due to chemotherapy induced thrombocytopenia

This study focused on the evolutionary relatedness and residual conservation between the closely related species of IL11. Mutational impact in human due to I171V, which was observed in four species (Urocitellus parryii, Otolemur garnettii, Lagenorhynchus obliquidens and Delphinapterus leucas) in the multiple sequence alignment, was examined. The mutations other than isoleucine were observed to be highly conserved. All the mutations preserved protein functionality. An overall decreasing thermodynamic stability was inferred for the protein with mutations: I171D, R190E and L194D along-with a deleterious effect. Non-deleterious effect was observed for R135E mutation with a comparatively more stable Gibbs free energy. However, I171D, I171V, R135E and R190E occur in protein's binding sites and have the potential to alter ligand efficiency and other binding properties of IL11. Four documented mutations showed a transition from helices to coils whereas I171V did not cause any such transition. Phylogenetic tree of IL11 proteins demonstrated evolutionary divergence among IL11 proteins of land and water animals. Human IL11 was the most closely related to Urocitellus parryii, an arctic ground squirrel. Hyperagonistic mutation (R135E) shall be in the limelight for it can lead IL11 to act as an efficient thrombopoietic peptide.
Source: Meta Gene - Category: Genetics & Stem Cells Source Type: research