ABSTRACT
Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species' blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors' lipid metabolism and/or bloodstream oxidative environment affecting PON1's role in fatty acid oxidation. PON1 loss also eliminates marine mammals' main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environments.
Subject(s)
Aryldialkylphosphatase/blood , Aryldialkylphosphatase/genetics , Cetacea , Evolution, Molecular , Lipid Metabolism , Metabolic Detoxication, Phase I , Organophosphorus Compounds/metabolism , Adaptation, Biological , Animals , Cetacea/blood , Cetacea/classification , Cetacea/genetics , Environmental Exposure , Genetic Fitness , Lipoproteins, HDL/metabolism , Lipoproteins, LDL/metabolism , Organophosphorus Compounds/toxicity , Oxidation-Reduction , Phylogeny , Risk , Selection, GeneticABSTRACT
The World Wide Web is an indispensable tool for biomedical researchers who are striving to understand the molecular basis of phenotype. However, it presents challenges in the form of proliferation of data resources, with heterogeneity ranging from their content to functionality to interfaces. This often frustrates researchers who must visit multiple sites, become familiar with their interfaces, and learn how to use them to extract knowledge. Even then, one may never feel sure that they have tracked down all needed information. We envision addressing this challenge with GNOMICS (Genomic Nomenclature Omnibus and Multifaceted Informatics and Computational Suite), a suite with both a programmatic interface and a GUI. GNOMICS allows for extensible biomedical functionality, including identifier conversion, pathway enrichment, sequence alignment, and reference gathering, among others. It combines usage of other biological and chemical database application programming interfaces (APIs) to deliver uniform data which can be further manipulated and parsed.
