A comprehensive phylogenetic analysis of the serpin superfamily

Matthew A. Spence, Matthew D. Mortimer, Ashley M. Buckle, Bui Quang Minh, Colin J. Jackson

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)


Serine protease inhibitors (serpins) are found in all kingdoms of life and play essential roles in multiple physiological processes. Owing to the diversity of the superfamily, phylogenetic analysis is challenging and prokaryotic serpins have been speculated to have been acquired from Metazoa through horizontal gene transfer due to their unexpectedly high homology. Here, we have leveraged a structural alignment of diverse serpins to generate a comprehensive 6,000-sequence phylogeny that encompasses serpins from all kingdoms of life. We show that in addition to a central "hub"of highly conserved serpins, there has been extensive diversification of the superfamily into many novel functional clades. Our analysis indicates that the hub proteins are ancient and are similar because of convergent evolution, rather than the alternative hypothesis of horizontal gene transfer. This work clarifies longstanding questions in the evolution of serpins and provides new directions for research in the field of serpin biology.

Original languageEnglish
Pages (from-to)2915-2929
Number of pages15
JournalMolecular Biology and Evolution
Issue number7
Publication statusPublished - Jul 2021


  • evolution
  • phylogenetics
  • serpin

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