4.8 Article

Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals

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SCIENCE
卷 361, 期 6402, 页码 591-+

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aap7714

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资金

  1. NIH [R01HG009299, U54 HG008540]
  2. NIH as part of the HHMI-NIBIB Interfaces Initiative [T32 EB009403]
  3. University of Washington, Division of Medical Genetics
  4. American Heart Association [16SDG30300009]
  5. Winifred Violet Scott Foundation
  6. Sea World Research and Rescue Foundation
  7. U.S. Geological Survey
  8. NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG009299, U54HG008540] Funding Source: NIH RePORTER
  9. NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [T32EB009403] Funding Source: NIH RePORTER

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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.

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