Domain Expansion and Functional Diversification in Vertebrate Reproductive Proteins |
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Authors: | Alberto M. Rivera Damien B. Wilburn Willie J. Swanson |
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Affiliation: | Department of Genome Sciences, University of Washington, Seattle, WA, USA;Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA |
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Abstract: | The rapid evolution of fertilization proteins has generated remarkable diversity in molecular structure and function. Glycoproteins of vertebrate egg coats contain multiple zona pellucida (ZP)-N domains (1–6 copies) that facilitate multiple reproductive functions, including species-specific sperm recognition. In this report, we integrate phylogenetics and machine learning to investigate how ZP-N domains diversify in structure and function. The most C-terminal ZP-N domain of each paralog is associated with another domain type (ZP-C), which together form a “ZP module.” All modular ZP-N domains are phylogenetically distinct from nonmodular or free ZP-N domains. Machine learning–based classification identifies eight residues that form a stabilizing network in modular ZP-N domains that is absent in free domains. Positive selection is identified in some free ZP-N domains. Our findings support that strong purifying selection has conserved an essential structural core in modular ZP-N domains, with the relaxation of this structural constraint allowing free N-terminal domains to functionally diversify. |
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Keywords: | fertilization gene duplication molecular evolution machine learning phylogenetics protein structure |
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