PUBLICATION
Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology
- Authors
- Brown, A.R., Gunnarsson, L., Kristiansson, E., Tyler, C.R.
- ID
- ZDB-PUB-141119-2
- Date
- 2014
- Source
- Philosophical transactions of the Royal Society of London. Series B, Biological sciences 369(1656): 2411-23 (Journal)
- Registered Authors
- Tyler, Charles R.
- Keywords
- drug target, orthologue, physiology, population ecology, species, susceptibility
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Biological Evolution
- Ecosystem
- Fishes/genetics*
- Fishes/physiology*
- Models, Biological
- Pharmaceutical Preparations/chemistry*
- Phylogeny
- Sequence Alignment
- Species Specificity
- Water Pollutants, Chemical/chemistry
- Water Pollutants, Chemical/toxicity*
- PubMed
- 25405965 Full text @ Phil. Trans. Roy. Soc. Lond., Series B
Citation
Brown, A.R., Gunnarsson, L., Kristiansson, E., Tyler, C.R. (2014) Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 369(1656):2411-23.
Abstract
Fish represent the planet's most diverse group of vertebrates and they can be exposed to a wide range of pharmaceuticals. For practical reasons, extrapolation of pharmaceutical effects from 'model' species to other fish species is adopted in risk assessment. Here, we critically assess this approach. First, we show that between 65% and 86% of human drug targets are evolutionarily conserved in 12 diverse fish species. Focusing on nuclear steroid hormone receptors, we further show that the sequence of the ligand binding domain that plays a key role in drug potency is highly conserved, but there is variation between species. This variation for the oestrogen receptor, however, does not obviously account for observed differences in receptor activation. Taking the synthetic oestrogen ethinyloestradiol as a test case, and using life-table-response experiments, we demonstrate significant reductions in population growth in fathead minnow and medaka, but not zebrafish, for environmentally relevant exposures. This finding contrasts with zebrafish being ranked as more ecologically susceptible, according to two independent life-history analyses. We conclude that while most drug targets are conserved in fish, evolutionary divergence in drug-target activation, physiology, behaviour and ecological life history make it difficult to predict population-level effects. This justifies the conventional use of at least a 10× assessment factor in pharmaceutical risk assessment, to account for differences in species susceptibility.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping