Tandem duplication of genes can play a critical role in the evolution of functional novelty, but our understanding is limited concerning gene duplication's role in coevolution between species. Much is known about the evolution and function of tandemly duplicated snake venom genes, however the potential of gene duplication to fuel venom resistance within prey species is poorly understood. In this study, we characterize patterns of gene duplication of the SERPINA subfamily of genes across in vertebrates and experimentally characterize functional variation in the SERPINA3-like paralogs of a wild rodent. We find the hallmarks of rapid birth-death evolution of SERPINA1-like and SERPINA3-like genes within and between rodent lineages. Next, we recombinantly expressed the 2 paralogous duplicates of SERPINA1 and 12 paralogous duplicates of SERPINA3 found in the genome of the big-eared woodrat (