Conserved Ser residues, the shutter region, and speciation in serpin evolution

Area of Science:

• Biochemistry
• Evolutionary Biology
• Molecular Biology

Background:

• The serpin superfamily of proteins are crucial serine protease inhibitors.
• Their inhibitory mechanism relies on structural flexibility, particularly in the breach and shutter regions of the central Abeta-sheet.
• Understanding the evolutionary pressures on serpins is key to comprehending their functional diversification.

Purpose of the Study:

• To investigate the evolutionary history of serpins by examining codon usage patterns.
• To determine if changes in serpin function or phylogenetic speciation drove their evolution.
• To analyze codon usage in highly conserved residues within the serpin shutter region.

Main Methods:

• Analysis of codon usage for specific serine residues (Ser-53 and Ser-56) in the shutter region of serpins.
• Comparison of codon usage patterns across different species, focusing on the protostome-deuterostome split.
• Phylogenetic analysis to correlate genetic patterns with evolutionary history.

Main Results:

• A distinct TCN-AGY codon usage dichotomy was identified for Ser-56.
• This codon usage pattern is strongly correlated with the evolutionary split between protostomes and deuterostomes.
• The findings indicate a significant link between genetic code usage and major evolutionary events.

Conclusions:

• Serpin evolution appears to be primarily driven by phylogenetic speciation events.
• The observed codon usage patterns suggest evolutionary constraints related to speciation rather than adaptation to new physiological functions.
• This challenges the notion of coevolution with serine proteases as the main driver of serpin diversification.