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Home / Equine Research Bank / PeerJ / Phylogenetic analysis of the cytochrome P450 (CYP450) nucleo...
PeerJ2018; 6; e5718; doi: 10.7717/peerj.5718

Phylogenetic analysis of the cytochrome P450 (CYP450) nucleotide sequences of the horse and predicted CYP450s of the white rhinoceros (Ceratotherium simum) and other mammalian species.

Abstract: The plight of the white rhinoceros () and the increasing need of treatment options for injured poaching victims led to the necessity to expand the knowledge on applicable drugs in this endangered species. With very little information available on drug pharmacokinetics in rhino, veterinarians have to rely on information generated from other species. The horse being a closely related species, has served as the model for dose extrapolations. However, from recent research on enrofloxacin and carprofen, the white rhino showed considerable differences in the pharmacokinetic properties of these drugs in comparison to the horse. While the reason for the differences is unknown, a likely cause may be a difference in present cytochrome P450 (CYP450), which may result in the rhino being genetically deficient in certain enzyme families. Methods: For this paper we assess the degree of similarity of the CYP genome sequences across the different species, using BLAT (BLAST-like alignment tool) for the alignment of the nucleotide sequences of the equine CYP450 with potential homologous nucleotide sequences of the published database from white rhinos and other mammalian species (cow, pig, dog, sheep, elephant, mouse and human). Results: The white rhino nucleotide sequences were 90.74% identical to the equine sequences. This was higher than the degree of similarity between any of the other evaluated species sequences. While no specific CYP family were found to be deficient in the published rhino genome, the horse genome contained additional genetic sequence for a larger number of iso-enzymes that were not present in the rhino. Conclusions: In pharmacokinetic study, it is well known that absence of a metabolic enzyme will result in constraints in drug metabolism and drug elimination. While this was our speculation, comparison to the horse and other mammalian species indicate that all the described CYP genes required for metabolism are present within the rhino genome. These results leave functional differences in enzyme activity and a lack of isoenzymes as the likely reason for the constraint in drug metabolism. Despite a more than 90% similarity of the equine and rhino gene sequences, seemingly small differences can have major effects on drug metabolism. Thus, in spite of the close anatomical relationship, the rhino should not simply be treated like a big horse.
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Publication Date: 2018-10-09 PubMed ID: 30324017PubMed Central: PMC6183514DOI: 10.7717/peerj.5718Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article presents a comparative study of the genetic sequences involved in drug metabolism within horses and white rhinoceroses, along with other mammalian species. It reveals a significant similarity, but also identifies fundamental differences, between the two closely related species that may explain variations in the effectiveness of drug treatment.

Objectives and Methodology

  • The primary objective of the study was to understand the reason behind the considerable difference in pharmacokinetic properties of drugs, such as enrofloxacin and carprofen, between horses and rhinos.
  • The researchers hypothesized that this difference might stem from variance in the presence of cytochrome P450 (CYP450), a family of enzymes crucial in drug metabolism.
  • To assess this, the authors compared the CYP genome sequences of various species using a BLAT (BLAST-like alignment tool).
  • This tool was used to align nucleotide sequences of the equine CYP450 with potentially similar sequences from rhinos and other mammals (cow, pig, dog, sheep, elephant, mouse, and human).

Findings

  • The analysis revealed that the nucleotide sequences of the white rhino were 90.74% identical to those of the horse, a higher degree of similarity than any other species in the study.
  • Contrary to the initial hypothesis, it was found that no specific CYP family was deficient in the published rhino genome.
  • However, it was observed that the horse genome contained additional genetic sequences for a larger number of iso-enzymes not present in the rhino genome.

Conclusion

  • Even a minor absence of a metabolic enzyme might result in significant constraints in drug metabolism and elimination.
  • Despite the similarity of over 90% between the genetic sequences of horses and rhinos, small differences can have a major impact on drug metabolism.
  • This implies that the lack of iso-enzymes or functional differences in enzyme activity might be responsible for the constraint in drug metabolism, contrary to the assumed deficiency in certain enzyme families.
  • Given these results, the study suggests that, despite their anatomical similarities, rhinos should not simply be treated like large horses when it comes to drug treatment.

Cite This Article

APA
Leiberich M, Marais HJ, Naidoo V. (2018). Phylogenetic analysis of the cytochrome P450 (CYP450) nucleotide sequences of the horse and predicted CYP450s of the white rhinoceros (Ceratotherium simum) and other mammalian species. PeerJ, 6, e5718. https://doi.org/10.7717/peerj.5718

Publication

PeerJ
ISSN: 2167-8359
NlmUniqueID: 101603425
Country: United States
Language: English
Volume: 6
Pages: e5718
PII: e5718

Researcher Affiliations

Leiberich, Marion
  • Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.
Marais, Hendrik Johannes
  • Saving the Survivors, Pretoria, South Africa.
Naidoo, Vinny
  • Department of Paraclinical Science, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 1 times.
  1. Karakus E, Prinzinger C, Leiting S, Geyer J. Sequencing of the Canine Cytochrome P450 CYP2C41 Gene and Genotyping of Its Polymorphic Occurrence in 36 Dog Breeds.. Front Vet Sci 2021;8:663175.
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