Analyzing the evolution of beta-endorphin post-translational processing events: studies on reptiles

Area of Science:

• Evolutionary biology
• Molecular biology
• Biochemistry

Background:

• Pro-opiomelanocortin (POMC) processing in many vertebrates involves monobasic cleavage of beta-endorphin.
• This cleavage yields an opioid peptide of 8-10 amino acids, dependent on a specific amino acid motif (-E-R-(S/G)-Q-).
• Mammals and birds lack this motif, suggesting evolutionary changes in beta-endorphin processing.

Purpose of the Study:

• To investigate the evolution of beta-endorphin post-translational processing in amniotes.
• To understand how the monobasic cleavage mechanism was lost in the lineage leading to mammals and birds.
• To identify the specific sequence changes responsible for the loss of beta-endorphin processing.

Main Methods:

• Cloning of POMC cDNA from the turtle, Chrysemys scripta.
• Comparative analysis of beta-endorphin sequences from various reptiles (turtles, gecko) and known bird and mammal sequences.
• Identification of amino acid motifs critical for monobasic cleavage.

Main Results:

• The beta-endorphin sequence from Chrysemys scripta was determined and compared to other reptiles, birds, and mammals.
• Analysis revealed that loss of the arginine residue or substitution at the glutamine position in the consensus sequence correlates with the absence of monobasic cleavage.
• Reptilian sequences show variations that explain the loss of this processing step.

Conclusions:

• The loss of beta-endorphin monobasic cleavage in amniotes is attributed to specific amino acid substitutions in the cleavage motif.
• These substitutions likely occurred in ancestral amniotes, predating the divergence of reptiles, birds, and mammals.
• Understanding these evolutionary changes provides insight into the diversification of peptide processing mechanisms.