Independent losses of a xenobiotic receptor across teleost evolution

Abstract

Sensitivity to environmental stressors largely depend on the genetic complement of the organism. Recent sequencing and assembly of teleost fish genomes enable us to trace the evolution of defense genes in the largest and most diverse group of vertebrates. Through genomic searches and in-depth analysis of gene loci in 76 teleost genomes, we show here that the xenosensor pregnane X receptor (Pxr, Nr1i2) is absent in more than half of these species. Notably, out of the 27 genome assemblies that belong to the Gadiformes order, the pxr gene was only retained in the Merluccidae family (hakes) and Pelagic cod (Melanonus zugmayeri). As an important receptor for a wide range of drugs and environmental pollutants, vertebrate PXR regulate the transcription of a number of genes involved in the biotransformation of xenobiotics, including cytochrome P450 enzymes (CYP). In the absence of Pxr, we suggest that the aryl hydrocarbon receptor (Ahr) have evolved an extended regulatory role by governing the expression of certain Pxr target genes, such as cyp3a, in Atlantic cod (Gadus morhua). However, as several independent losses of pxr have occurred during teleost evolution, other lineages and species may have adapted alternative compensating mechanisms for controlling crucial cellular defense mechanisms.

Evolutionary Plasticity in Detoxification Gene Modules: The Preservation and Loss of the Pregnane X Receptor in Chondrichthyes Lineages

“…The occurrence of different gene complements of the NR1I subfamily in Chondrichthyes parallels similar findings in other vertebrate lineages [11,30,31]. Recently, an extensive investigation into 76 fish genomes suggests that approximately half of these species have lost PXR [11], in line with the description made here in cartilaginous fishes.…”

“…The occurrence of different gene complements of the NR1I subfamily in Chondrichthyes parallels similar findings in other vertebrate lineages [11,30,31]. Recently, an extensive investigation into 76 fish genomes suggests that approximately half of these species have lost PXR [11], in line with the description made here in cartilaginous fishes. Moreover, xenobiotic exposure experiments with classical xenobiotics, PXR ligands in cod ( PXR -absent) did not show a clear transcription activation of gene coding for P450 cytochrome enzymes ( CYP3A ), as observed in mice or zebrafish [11].…”

“…Moreover, PXR is notoriously involved in other metabolic processes including energy homeostasis, inflammatory responses, cell proliferation, apoptosis, and tumour development [5,6,7]. The taxonomic distribution of VDR/PXR/CAR gene orthologs is remarkably mutable [8,9,10,11]. In vertebrate species, VDR is found in both cyclostomes (lampreys) and gnathostomes [12]; CAR occurs in tetrapods [10,13]; while PXR genes have been described and characterized in amphibians [10] and mammals [10].…”

“…In vertebrate species, VDR is found in both cyclostomes (lampreys) and gnathostomes [12]; CAR occurs in tetrapods [10,13]; while PXR genes have been described and characterized in amphibians [10] and mammals [10]. On the other hand, teleost genomes, such as zebrafish ( Danio rerio ), also retain PXR , but this is not an universal condition found throughout teleost lineages [10,11], consistent with the highly derived nature of their genomes [14]. Importantly, synteny supports the hypothesis that the absence of PXR in birds, reptiles, and some teleosts, as well as CAR in ray-finned fish, is due to secondary gene loss [10].…”

ReCodLiver0.9: Overcoming challenges in genome-scale metabolic reconstruction of a non-model species

“…53 The Atlantic cod has lost the MHC II and related genes of the adaptive immune 54 system [48]. Furthermore, we have recently shown that cod, together with several other 55 teleost fish, have lost the pregnane x receptor (pxr, nr1i2 ) gene from their genomes [15]. 56 This xenosensor is activated by a wide range of drugs and pollutants, and regulates the 57 transcription of genes involved in all phases of the xenobiotic and steroid 58 biotransformation [29].…”