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

Abstract

<p class="first" id="P2">Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes including losses of protein function. While not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. Here we use phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, <i>Paraoxonase 1</i> ( <i>PON1</i>) 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. </p><p id="P3">Organophosphate toxicity may threaten modern marine mammals due to their ancestors’ repeated loss of PON1 for oxidative or metabolic reasons. </p>