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Water flea genome offers revolution in toxicity testing

February 3, 2011 By Virginia Gewin This article courtesy of Nature News.

DNA sequence of could help scientists to probe the environment and test chemicals.

The genome of the water flea Daphnia pulex has been sequenced for the first time. Its DNA code contains the largest number of genes ever recorded for a multicellular animal, and could help boost efforts to test the toxicity of chemicals or environmental pollutants without the need for experiments on rats or mice.

Daphnia is a small algae-grazing crustacean found in water all over the world and an important food source for fish. The authors of a study published today in Science1 have identified 30,907 genes packed into its genome, more than one-third of which are undocumented in any other organism.

The findings promise to usher in a new era of ecotoxicology.

Scientists are eager to develop ways to use gene expression profiles to pinpoint toxins that pose a risk to the environment or to human health because they will be quicker and cheaper than testing thousands of chemicals on lab rats. But until now, gene-expression studies have been constrained mainly to traditional model organisms whose genomes have been sequenced, such as fruit fly (Drosophila melanogaster) or mouse (Mus musculus).

This is less than ideal, because "the genes that matter most to ecological geneticists are difficult to uncover in traditional model organisms kept under controlled laboratory conditions", says John Colbourne, genomics director of the Center for Genomics and Bioinformatics at Indiana University in Bloomington and lead author of the study. Daphnia, however, is an ecologically-relevant model organism that, with the genome in hand, will allow scientists to probe the environment.

Regulatory reality?

Colbourne is a founding member of the Daphnia Genomics Consortium, a 450-member international research collective based at Indiana University, which aims to develop cheap, fast screening tools to identify toxins of greatest concern to the environment and human health. The organism that forms their focus has been used by environmental protection agencies to set regulatory limits on pollution for more than 50 years due to its short life cycle, ubiquity and sensitivity to toxins.

Some 80,000 chemicals are registered for us in the United States, yet less than 1% of those have undergone rigorous safety testing. The US Environmental Protection Agency and the European Chemicals Agency, based in Helsinki, are developing strategies to rapidly screen chemicals that may pose a risk to human health and the environment — with the goal of limiting vertebrate animal testing.

Wim De Coen of the European Chemicals Agency says that now the water flea's genetic code is known, gene-expression tools based on the creature could be used widely in programmes such as the European Commission's REACH regulation for chemicals and their safe use. But first, researchers must conduct enough studies to create a reference database linking specific adverse effects to gene-expression profiles.

The challenge is that, to be useful to regulators, the science needs to be distilled into simple metrics that can easily be used to judge risk or safety. "It would be a shame if regulators and scientists don't follow up and build these missing bridges within the next decade," says De Coen.

Daphnia has unusual biology that could be used to build these bridges quickly. For example, Daphnia eggs can lay dormant in sediments for hundreds of years, so scientists may also be able to trace past population-level adaptations to environmental stresses, such as metal toxicities from mining.

The crustacean can also clone itself, so ecologists will be able to expose individual genetically identical water fleas to different environmental stressors and track changes in their gene expression. "We are entering a phase where we can effectively conduct 'twin studies' — a sophisticated strategy not possible until now," says evolutionary biologist Dieter Ebert, a visiting fellow at the Institute for Advanced Study in Berlin.

It is less clear how useful Daphnia-based genomic tools will be for screening chemicals for their risk to human health, says John Bucher, associate director of the US National Toxicology Program.

In 2008, Bucher and Francis Collins — then director of the National Human Genome Research Institute in Bethesda, Maryland, now director of the National Institutes of Health — laid out a strategy to phase out toxicity assessments based on vertebrate studies2. The idea was to switch to invertebrate model organisms or computational models, but Daphnia gene-expression profiles are not what Bucher and Collins had in mind.

But Colbourne stresses the positives of Daphnia models. His study indicates that, in comparison with other invertebrates, Daphnia has a high proportion of genes in common with humans. "By sharing many genes with humans, and because of its sentinel role in freshwater food webs, Daphnia's stress-specific gene-expression profiles may someday serve at the interface of protecting both human and ecosystem health," he says.


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