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Cross-species evaluation of molecular target sequence and structural conservation as a line of evidence for identification of susceptible taxa to inform derivation of aquatic life criteria
Citation:
LaLone, C., Dan Villeneuve, AND G. Ankley. Cross-species evaluation of molecular target sequence and structural conservation as a line of evidence for identification of susceptible taxa to inform derivation of aquatic life criteria. SETAC North America, Orlando, FL, November 06 - 10, 2016.
Impact/Purpose:
not applicable
Description:
The 1985 U.S. Environmental Protection Agency (EPA) Guidelines for Deriving Aquatic Life Criteria (ALC) require acute and chronic toxicity testing with a fixed list of taxa that cover aquatic organisms from vertebrates, invertebrates, and plants. In considering Guideline revisions, there is interest in employing new and readily available technologies to inform chemical-specific selection of test species based on scientific evidence for susceptibility as a means to eliminate unnecessary animal testing, reduce cost, and gain the most applicable data for decision making. Further, when toxicity testing is completed on selected organisms, advances in methods for species extrapolation could be implemented to gain a greater understanding of how representative the data are of other species from the same taxonomic group. A publically available computational application for informing such considerations is the U.S EPA’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) tool. SeqAPASS facilitates cross species comparisons of chemical molecular targets based on evaluation of protein similarity. The underlying assumption is that if a chemical is known to act on a specific protein to initiate toxicity in one species, conservation of that protein in another species provides a line of evidence that the second species could also be susceptible to a given chemical. Depending on the degree of characterization of the selected protein and existing knowledge about the chemical-protein interaction, SeqAPASS derives susceptibility predictions by evaluating similarity from alignments of primary amino acid sequences, functional domains (e.g., ligand-binding domain), and individual amino acid residue(s) important for maintaining protein structure or for direct interaction with the chemical. Such data can be used to identify species that are likely (or unlikely) susceptible to a given chemical, therefore aiding in selection of appropriate test species. Additionally the data would be useful in understanding how broadly toxicity test data derived from one species may be extrapolated to others. In short, evaluation of cross species protein and structural conservation using SeqAPASS provides a rapid and cost effective method for deriving a line of evidence for chemical-specific testing strategies that may be useful in the revised ALC Guidelines.