The dopamine receptor D₅gene shows signs of independent erosion in Toothed and Baleen whales

Abstract

To compare gene loci considering a phylogenetic framework is a promising approach 11 to uncover the genetic basis of human diseases. Imbalance of dopaminergic systems is suspected 12 to underlie some emerging neurological disorders. The physiological functions of dopamine are 13 transduced via G-protein-coupled receptors, including DRD5 which displays a relatively higher 14 affinity towards dopamine. Importantly, DRD5 knockout mice are hypertense, a condition 15 emerging from an increase in sympathetic tone. We investigated the evolution of DRD5, a high 16 affinity receptor for dopamine, in mammals. Surprisingly, among 124 investigated mammalian 17 genomes, we found that Cetacea lineages (Mysticeti and Odontoceti) have independently lost this 18 gene, as well as the burrowing Chrysochloris asiatica (Cape golden mole). We suggest that DRD5 19 inactivation parallels hypoxia-induced adaptations, such as peripheral vasoconstriction required 20 for deep-diving in Cetacea, in accordance with the convergent evolution of vasoconstrictor genes 21 in hypoxia-exposed animals. Our findings indicate that Cetacea are natural knockouts for DRD5 22 and might offer valuable insights into the mechanisms of some forms of vasoconstriction 23 responses and hypertension in humans.24

Psychosocial Stress and Cannabinoid Drugs Affect Acetylation of α-tubulin (K40) and Gene Expression in the Prefrontal Cortex of Adult Mice

“…Indeed, exposure to either psychosocial stress or acute administration of the inverse agonist acted in the opposite direction than the cannabinoid agonist did 85,92 . Dopaminergic neurotransmission is essential for cerebral function, controlling various physiological mechanisms including cognition, locomotion, neuroendocrine activity, emotional and motivational aspects 93 . Recent studies have demonstrated that midbrain dopaminergic neurons are particularly vulnerable to microtubule disruptions 94 .…”