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PreprintCited by 8Protease and Inhibitor MechanismsGenomics and Phylogenetic StudiesChromosomal and Genetic Variations

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Origin and early diversification of the papain family of cysteine peptidases

Open access
Kordiš, Dušan, Turk, Vito·2023·International Journal of Molecular Sciences
DOI 10.20944/preprints202306.1638.v1PMC PMC10380794

Preprint — published as 10.3390/ijms241411761 · Paper page

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Abstract

Peptidases of the papain family play a key role in protein degradation, regulated proteolysis, and the host-pathogen arms race. Although the papain family has been the subject of many studies, knowledge about its diversity, origin, and evolution in Eukaryota, Bacteria, and Archaea is limited; thus, we aimed to answer these long-standing questions. We traced the origin and expansion of the papain family through phylogenomic analysis, using sequence data from numerous prokaryotic and eukaryotic proteomes, transcriptomes, and genomes. We identified the full complement of the papain family in all prokaryotic and eukaryotic lineages. Analysis of the papain family provided strong evidence for its early diversification in the ancestor of eukaryotes. We found that the papain family has undergone complex and dynamic evolution through numerous gene duplications, which produced eight eukaryotic ancestral paralogous C1A lineages during eukaryogenesis. Different evolutionary forces operated on C1A peptidases, including gene duplication, horizontal gene transfer, and gene loss. This study challenges the current understanding of the origin and evolution of the papain family and provides valuable insights into their early diversification. The findings of this comprehensive study provide guidelines for future structural and functional studies of the papain family.

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Crossref · 10.20944/preprints202306.1638.v1

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Figures

Figure 1 Early diversification of the papain family in the eukaryotic ancestor. The rooted ML tree shows the evolutionary relationships between the seven ancestral eukaryotic orthologous gene families, cathepsins B, C, X, L, H, and F, and the 26/29 kDa peptidase. The best-fit model, according to the Bayesian information criterion, was WAG + I + G4. The ML tree represents bootstrap consensus following 1000 replicates. Sequences were obtained from GenBank, and species names and accession numbers are included.
Figure 1 Early diversification of the papain family in the eukaryotic ancestor. The rooted ML tree shows the evolutionary relationships between the seven ancestral eukaryotic orthologous gene families, cathepsins B, C, X, L, H, and F, and the 26/29 kDa peptidase. The best-fit model, according to the Bayesian information criterion, was WAG + I + G4. The ML tree represents bootstrap consensus following 1000 replicates. Sequences were obtained from GenBank, and species names and accession numbers are included.CC BY · PubMed Central
Figure 2 ML tree for the eukaryote-specific type 1 long C1 peptidases. The midpoint-rooted ML tree shows the evolutionary relationships inside the eukaryote-specific type 1 long C1 peptidases. The best-fit model, according to the Bayesian information criterion, was PMB + F + I + G4. The ML tree represents the bootstrap consensus following 1000 replicates. Sequences were obtained from GenBank, and species names and accession numbers are included. Abbreviations: T_vaginalis: Trichomonas vaginalis; Trit_foetus: Tritrichomonas foetus; E_histolytica: Entamoeba histolytica.
Figure 2 ML tree for the eukaryote-specific type 1 long C1 peptidases. The midpoint-rooted ML tree shows the evolutionary relationships inside the eukaryote-specific type 1 long C1 peptidases. The best-fit model, according to the Bayesian information criterion, was PMB + F + I + G4. The ML tree represents the bootstrap consensus following 1000 replicates. Sequences were obtained from GenBank, and species names and accession numbers are included. Abbreviations: T_vaginalis: Trichomonas vaginalis; Trit_foetus: Tritrichomonas foetus; E_histolytica: Entamoeba histolytica.CC BY · PubMed Central
Figure 3 AlphaFold-predicted structures of the two ancestral C1A lineages. (A) AlphaFold-predicted structure of the type 1 long C1 peptidase from Phytophthora infestans (A0A833SVU0_PHYIN). The transmembrane domain is located at positions 32–53. (B) AlphaFold-predicted structure of the 26/29 kDa peptidase from Aedes albopictus (midgut cysteine proteinase 2; A0A182HAH0_AEDAL).
Figure 3 AlphaFold-predicted structures of the two ancestral C1A lineages. (A) AlphaFold-predicted structure of the type 1 long C1 peptidase from Phytophthora infestans (A0A833SVU0_PHYIN). The transmembrane domain is located at positions 32–53. (B) AlphaFold-predicted structure of the 26/29 kDa peptidase from Aedes albopictus (midgut cysteine proteinase 2; A0A182HAH0_AEDAL).CC BY · PubMed Central

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Metadata

Authors
Kordiš, D., & Turk, V.
Affiliations
Jožef Stefan Institute (SI)
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-06-22
Volume
24
Issue
14
Pages
11761-11761
ISSN
1422-0067 (ISSN-L)
DOI
10.20944/preprints202306.1638.v1
PMC
PMC10380794
OpenAlex
W4385172689
Cited by
8
References
1
Citations by year
2025: 2 · 2024: 3 · 2023: 3
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Javna Agencija za Raziskovalno Dejavnost RS (P1-0207, P1-0140, J1-2473)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords
papain family, cysteine peptidases, protein evolution, eukaryotic origin, gene duplication, horizontal gene transfer, gene loss, host-pathogen arms race, protein degradation
MeSH terms
Archaea, Cysteine, Papain, Peptide Hydrolases, Phylogeny, Evolution, Molecular, Eukaryota, Cysteine Proteases

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