Journal of Molecular Evolution

, Volume 85, Issue 3–4, pp 137–157 | Cite as

Tracing the Evolutionary History of the CAP Superfamily of Proteins Using Amino Acid Sequence Homology and Conservation of Splice Sites

Original Article


Proteins of the CAP superfamily play numerous roles in reproduction, innate immune responses, cancer biology, and venom toxicology. Here we document the breadth of the CAP (Cysteine-RIch Secretory Protein (CRISP), Antigen 5, and Pathogenesis-Related) protein superfamily and trace the major events in its evolution using amino acid sequence homology and the positions of exon/intron borders within their genes. Seldom acknowledged in the literature, we find that many of the CAP subfamilies present in mammals, where they were originally characterized, have distinct homologues in the invertebrate phyla. Early eukaryotic CAP genes contained only one exon inherited from prokaryotic predecessors and as evolution progressed an increasing number of introns were inserted, reaching 2–5 in the invertebrate world and 5–15 in the vertebrate world. Focusing on the CRISP subfamily, we propose that these proteins evolved in three major steps: (1) origination of the CAP/PR/SCP domain in bacteria, (2) addition of a small Hinge domain to produce the two-domain SCP-like proteins found in roundworms and anthropoids, and (3) addition of an Ion Channel Regulatory domain, borrowed from invertebrate peptide toxins, to produce full length, three-domain CRISP proteins, first seen in insects and later to diversify into multiple subtypes in the vertebrate world.


Cysteine-rich protein superfamily CRISP protein family Phylogenetic analysis Splice sites 



We would like to thank Dr. Kenneth Buetow for fruitful discussions on CAP protein evolution during our study and Stuart Newfeld for advice on phylogenetic tree construction. We would also like to thank the National Science Foundation for support of our previous studies of allurin, a truncated CRISP protein having sperm chemoattractant activity, which led to our interest in the evolution of CAP proteins.

Supplementary material

239_2017_9813_MOESM1_ESM.pptx (3.1 mb)
Supplementary material 1 (PPTX 3176 KB)


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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.School of Life SciencesArizona State UniversityTempeUSA

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