Evolution of the mammalian insulin (Ins) gene; Changes in proteolytic processing

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Insulin signaling disruption causes diabetes in humans, but some species tolerate functional changes.
• Mammalian genomes offer insights into insulin gene evolution and function.

Purpose of the Study:

• To identify and analyze mammalian insulin (Ins) gene sequences from public databases.
• To investigate potential variations in insulin processing and receptor interaction sites across species.

Main Methods:

• Bioinformatic analysis of 156 mammalian genomes for complete Ins coding sequences.
• Identification of duplicated Ins genes in rodents.
• Prediction of signal peptides and analysis of substitutions at prohormone convertase and insulin receptor binding sites.

Main Results:

• 161 complete mammalian Ins coding sequences were identified from 151 species.
• Duplicated Ins genes were found in 12 rodent species.
• Substitutions at critical processing sites were observed in 6 species (2 bats, 4 Afrotheria), suggesting impaired insulin processing.
• Significant substitutions at insulin receptor interaction sites were noted in two bat species (Myotis brandtii, M. lucifugus).

Conclusions:

• Mammalian insulin genes exhibit significant diversity in processing sites and potential receptor interactions.
• Variations in insulin processing may allow some species to tolerate functional changes without developing diabetes.
• Further research is needed to understand the functional implications of these identified insulin sequence variations.