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Reconstruction of Cyclooxygenase Evolution in Animals Suggests Variable, Lineage-Specific Duplications, and Homologs with Low Sequence Identity

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Abstract

Cyclooxygenase (COX) enzymatically converts arachidonic acid into prostaglandin G/H in animals and has importance during pregnancy, digestion, and other physiological functions in mammals. COX genes have mainly been described from vertebrates, where gene duplications are common, but few studies have examined COX in invertebrates. Given the increasing ease in generating genomic data, as well as recent, although incomplete descriptions of potential COX sequences in Mollusca, Crustacea, and Insecta, assessing COX evolution across Metazoa is now possible. Here, we recover 40 putative COX orthologs by searching publicly available genomic resources as well as ~250 novel invertebrate transcriptomic datasets. Results suggest the common ancestor of Cnidaria and Bilateria possessed a COX homolog similar to those of vertebrates, although such homologs were not found in poriferan and ctenophore genomes. COX was found in most crustaceans and the majority of molluscs examined, but only specific taxa/lineages within Cnidaria and Annelida. For example, all octocorallians appear to have COX, while no COX homologs were found in hexacorallian datasets. Most species examined had a single homolog, although species-specific COX duplications were found in members of Annelida, Mollusca, and Cnidaria. Additionally, COX genes were not found in Hemichordata, Echinodermata, or Platyhelminthes, and the few previously described COX genes in Insecta lacked appreciable sequence homology (although structural analyses suggest these may still be functional COX enzymes). This analysis provides a benchmark for identifying COX homologs in future genomic and transcriptomic datasets, and identifies lineages for future studies of COX.

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Acknowledgments

This work was supported by National Science Foundation grants Assembling the Tree of Life (DEB #1036537) and Antarctic Organisms and Ecosystems (ANT#1043745) to K.M.H. and S.R.S. and National Aeronautics and Space Administration grant NNX13AJ31G to K.M.H. and K.M.K. This represents contributions #127 and #32 to the Auburn University (AU) Marine Biology Program and Molette Biology Laboratory for Environmental and Climate Change Studies, respectively.

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  1. Justin C. Havird

    Present address: Department of Biology, Colorado State University, Fort Collins, CO, USA

  2. Kevin M. Kocot

    Present address: School of Biological Sciences, The University of Queensland, Brisbane, Australia

  3. Johanna T. Cannon

    Present address: Department of Zoology, Naturhistoriska riksmuseet, Stockholm, Sweden

  4. David A. Weese

    Present address: Department of Biological and Environmental Sciences, Georgia College and State University, Milledgeville, USA

Authors and Affiliations

  1. Department of Biological Sciences & Molette Biology Laboratory for Environmental and Climate Change Studies, Auburn University, Auburn, USA

    Justin C. Havird, Kevin M. Kocot, Pamela M. Brannock, Johanna T. Cannon, Damien S. Waits, David A. Weese, Scott R. Santos & Kenneth M. Halanych

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  1. Justin C. Havird
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Correspondence to Justin C. Havird.

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GenBank Accession Numbers KM437900-KM437941.

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Online Resource 1 Publically available datasets that were searched for cyclooxygenase sequences (XLS 41 kb)

Online Resource 2 Novel transcriptomic data for 250 taxa that were searched for cyclooxygenase sequences (XLS 72 kb)

239_2015_9670_MOESM3_ESM.xls

Online Resource 3 Table of cyclooxygenase (COX) sequences that were acquired from previous studies or public databases (XLS 38 kb)

Online Resource 4 Table of cyclooxygenase (COX) sequences that were identified as possible rogue sequences (XLS 33 kb)

239_2015_9670_MOESM5_ESM.eps

Online Resource 5 Bayesian inference (BI) phylogeny generated with PhyloBayes for 121 non-rogue cyclooxygenase (COX) and outgroup amino acid sequences used in the current analysis based on majority rule (50%). Run parameters, color schemes, shading, and scale bar as in Fig. 2. See Online Resource 7 for relationships among vertebrate COX sequences (EPS 1274 kb)

239_2015_9670_MOESM6_ESM.eps

Online Resource 6 Bayesian inference (BI; left) and maximum likelihood (ML; right) topologies for all Vertebrata/Craniata cyclooxygenase (COX) amino acid sequences used in the current analysis based on majority rule (50%). Run parameters, color schemes, shading, and scale bar are as in Figs. 1 and 2, with the exception that bolded/underlined sequences correspond to those obtained from public sources, but lacking in previous phylogenetic analyses of COX (EPS 1626 kb)

239_2015_9670_MOESM7_ESM.eps

Online Resource 7 Bayesian inference (BI; left) and maximum likelihood (ML; right) topologies for non-rogue Vertebrata/Craniata cyclooxygenase (COX) amino acid sequences used in the current analysis based on majority rule (50%). Run parameters, color schemes, shading, and scale bar are as in Figs. 1 and 2, with the exception that bolded/underlined sequences correspond to those obtained from public sources, but lacking in previous phylogenetic analyses of COX. (EPS 1560 kb)

239_2015_9670_MOESM8_ESM.xlsx

Online Resource 8 Maximum likelihood topology based on majority rule (50%) for all cyclooxygenase (COX) amino acid sequences used in the current analysis as well as the previously described functional red alga COX sequences (shown in red). Run parameters, scale bar, support values, etc. are the same as in Fig. 1. See Fig. 1 for relationships among terminal groups (XLSX 12 kb)

239_2015_9670_MOESM9_ESM.eps

Online Resource 9 The modelled structure of louse COX-1 (red) superimposed on the experimentally determined x-ray structure of sheep COX-1 (accession# 1DIY in the RCSB protein data bank, shown in blue). A general similarity between secondary structural elements suggests louse COX-1 may be functional, despite a lack of sequence homology to other COXs (EPS 791 kb)

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Online Resource 10 Table of TM scores showing similarity between the experimentally determined x-ray structure of sheep COX-1 (accession# 1DIY in the RCSB protein data bank 1DIY) and a subset of modelled COX structures for sequences described here. TM scores closer to 1 indicate a greater similarity between structures. As red alga COX has been biochemically shown to be functional, structures with similar or better TM scores may also suggest functional sequences (TIFF 160 kb)

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Havird, J.C., Kocot, K.M., Brannock, P.M. et al. Reconstruction of Cyclooxygenase Evolution in Animals Suggests Variable, Lineage-Specific Duplications, and Homologs with Low Sequence Identity. J Mol Evol 80, 193–208 (2015). https://doi.org/10.1007/s00239-015-9670-3

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