Tandem Duplication of Serpin Genes Yields Functional Variation and Snake Venom Inhibitors

Area of Science:

• Evolutionary biology
• Genomics
• Biochemistry

Background:

• Gene duplication is crucial for functional novelty and species coevolution.
• While snake venom gene evolution is studied, prey resistance mechanisms via gene duplication are less understood.
• The SERPINA gene subfamily encodes serine protease inhibitors, with SERPINA1 known to inhibit snake venom proteases.

Purpose of the Study:

• To investigate gene duplication patterns in the SERPINA gene family across species.
• To explore the role of SERPINA gene copy number evolution in prey venom resistance.
• To functionally characterize SERPINA3 paralogs from the Big-eared woodrat (Neotoma macrotis) for venom inhibition.

Main Methods:

• Comparative genomic analysis of SERPINA gene copy number evolution in rodents.
• Recombinant expression of 12 SERPINA3 paralogs from Neotoma macrotis.
• In vitro assays to assess the inhibitory activity of SERPINA3 paralogs against snake venom serine proteases.

Main Results:

• Identified rapid birth-death evolution and diversifying selection in SERPINA1-like and SERPINA3-like genes within rodent lineages.
• Demonstrated that two SERPINA3 paralogs from Neotoma macrotis inhibit snake venom serine proteases, acting as resistance factors.
• Observed functional variation among SERPINA3 paralogs, including neofunctionalization for simultaneous inhibition of different protease types.

Conclusions:

• Rapid SERPINA gene copy number evolution in rodents is linked to adaptive potential for venom resistance.
• Functionally diverse SERPINA paralogs contribute to prey defense against snake venoms.
• SERPINA gene duplication provides a mechanism for coevolutionary arms races between predators and prey.