The RAS subfamily Evolution – tracing evolution for its utmost exploitation

Abstract

In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub family information in scanty. Thus, a subfamily evolutionary study on RAS evolutionary expansion is imperative as it will aid in better drug designing against dreadful diseases like Cancer and other developmental diseases. The present study was aimed to understand RAS evolution on both holistic as well as reductive level. All human RAS family genes and protein were subjected to BLAST tools to find orthologs and paralogs with different parameters followed by phylogenetic tree generation. Our results clearly showed that H-RAS is the most primitive RAS in higher eukaryotes and then diverged into other RAS family members due to different gene modification events. Furthermore, a site specific selection pressure analysis was carried out using SELECTON server which showed that H-RAS, M-RAS and N-RAS are evolving faster than K-RAS and R-RAS. Thus, the results ascertain a new ground to cancer biologists to exploit negatively selected K-RAS and R-RAS as potent drug targets in cancer therapeutics.

Ras subfamily GTPases regulate development, aflatoxin biosynthesis and pathogenicity in the fungus Aspergillus flavus

“…As a prototypical member of the small GTPase family, the Ras subfamily is one of the most widely studied protein families (Saad et al, 2014). Ras evolutionary relationships have been studied mainly at the superfamily level (Saad et al, 2014), but there is little information about Ras subfamilies in filamentous fungi and no previous study has reported the functions of Ras subfamily protein in A. flavus. In this study, we found that the six Ras subfamily proteins of A. flavus were homologues and highly conserved in Aspergillus spp.…”

Effect of Cyclophilin from Pyropia Yezoensis on the Proliferation of Intestinal Epithelial Cells by Epidermal Growth Factor Receptor/Ras Signaling Pathway

“…[26]. The Ras/ERK biochemical cascade is the important mediator for growth factor-dependent cell survival, proliferation, and differentiation [26,27,28]. Especially, Cyp is known to affect ERK signaling activation [29].…”

Water in Ras Superfamily Evolution

“…Despite the common core domain structure and catalytic function, each subfamily is associated with unique cellular outcomes. The Ras subfamily regulates cellular proliferation and survival, with HRas being the most ancient subfamily member . The Rho subfamily regulates cell morphology, actin cytoskeletal organization, and cell migration .…”