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The RAS subfamily Evolution - tracing evolution for its utmost exploitation.

Ismail If Saad1, Saurav B Saha2, George Thomas3

  • 1Department of Zoology, Faculty of Science, Omar Al Mukhtar University, Al Bayda, Libya.

Bioinformation
|June 27, 2014
PubMed
Summary

This study reveals the evolutionary path of RAS proteins, identifying H-RAS as the most ancient. Faster evolution in H-RAS, M-RAS, and N-RAS contrasts with slower evolution in K-RAS and R-RAS, suggesting new cancer drug targets.

Keywords:
RAScancerevolutionevolutionary treeselection pressure

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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Genomics

Background:

  • Signaling proteins, particularly the RAS family, are crucial for multicellularity.
  • Previous evolutionary studies focused on the RAS superfamily, leaving subfamily details scarce.
  • Understanding RAS subfamily evolution is vital for developing targeted therapies for cancer and developmental diseases.

Purpose of the Study:

  • To investigate the evolutionary expansion of the RAS protein family.
  • To analyze RAS evolution at both holistic and reductive levels.
  • To identify potential drug targets within the RAS family for cancer therapeutics.

Main Methods:

  • Utilized BLAST tools to identify orthologs and paralogs of human RAS genes and proteins.
  • Generated phylogenetic trees to illustrate evolutionary relationships.
  • Performed site-specific selection pressure analysis using the SELECTON server.

Main Results:

  • Identified H-RAS as the most primitive RAS protein in higher eukaryotes.
  • Demonstrated divergence of RAS family members from H-RAS through gene modification events.
  • Found that H-RAS, M-RAS, and N-RAS exhibit faster evolutionary rates compared to K-RAS and R-RAS.

Conclusions:

  • The evolutionary trajectory of RAS proteins provides insights into their functional diversification.
  • K-RAS and R-RAS, under negative selection, represent promising targets for cancer drug development.
  • This research offers a new foundation for cancer biologists in targeting specific RAS proteins.