Rapid molecular evolution across amniotes of the IIS/TOR network

Area of Science:

• Evolutionary biology
• Genomics
• Molecular biology

Background:

• The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network is crucial for regulating lifespan, reproduction, metabolic diseases, cancer, and aging.
• Comparative analyses of the IIS/TOR network have been largely restricted to invertebrates and mammals, leaving significant gaps in our understanding of its evolution across vertebrates.

Purpose of the Study:

• To conduct an extensive evolutionary analysis of the IIS/TOR network across 66 amniotes, including newly generated transcriptomes from nonavian reptiles.
• To investigate molecular evolution, evolutionary rates, and signatures of selection within the IIS/TOR network in reptiles and mammals.

Main Methods:

• Generated 18 new transcriptomes from nonavian reptiles.
• Performed evolutionary analysis of the IIS/TOR network across 66 amniotes using available genomes and transcriptomes.
• Analyzed evolutionary rates of IIS/TOR genes, including critical nodes like insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K).
• Identified signatures of positive selection and coevolution within the IIS/TOR extracellular network.

Main Results:

• Uncovered rapid and extensive molecular evolution of the IIS/TOR network between reptiles and mammals.
• Observed divergent evolutionary rates for IIS/TOR network genes, with extracellular network genes exhibiting exceptionally fast rates compared to the rest of the genome.
• Found evidence of positive selection and coevolution, particularly on hormone-receptor binding surfaces (IGF1, IGF1R, INSR in reptiles; IGF2 in mammals) and reptile IGF2R.
• Suggests that key IIS/TOR paralogs have undergone sub- or neofunctionalization between reptiles and mammals.

Conclusions:

• The IIS/TOR network shows significant molecular evolution and adaptation between reptiles and mammals.
• Accelerated evolution and positive selection on hormone-receptor binding sites indicate functional divergence in IIS/TOR signaling pathways.
• These evolutionary changes likely contribute to fundamental life history and physiological differences observed between these major amniote sister clades.