Rapid reduction of Paraoxonase expression followed by inactivation across semiaquatic mammals suggests adaptive benefit of gene loss

Convergent adaptation to the same environment by multiple lineages frequently involves rapid evolutionary change at the same genes, implicating these genes as important for environmental adaptation. Such adaptive molecular changes may yield either change or loss of function; loss of protein function can eliminate newly deleterious proteins or reduce energy necessary for protein production. We previously found a striking case of recurrent pseudogenization of the Paraoxonase 1 (Pon1) gene among aquatic mammal lineages – Pon1 became a pseudogene at least six times independently in aquatic and semiaquatic mammals with clear genetic lesions, such as stop codons and frameshifts. Here, we assess the landscape and pace of pseudogenization by studying Pon1 sequences, expression levels, and blood plasma activity across four major aquatic and semiaquatic mammal lineages: pinnipeds, cetaceans, otters, and beavers. We also observed in beavers and pinnipeds an unexpected reduction in expression of Pon3, a paralog with similar expression patterns but different substrate preferences. Ultimately, in all lineages with aquatic/semiaquatic members, we find that preceding any coding level pseudogenization events in Pon1, there is a drastic decrease in expression, followed by relaxed selection, thus allowing for accumulation of disrupting mutations. The recurrent and rapid loss of Pon1 even suggests that it is adaptive in aquatic mammals. Accordingly, we examined diving and dietary traits across pinniped species as potential driving forces of Pon1 loss. We found that loss is best correlated with diving activity and is likely the result of selective pressures associated with hypoxia and hypoxia-induced inflammation.