The Preservation of PPARγ Genome Duplicates in Some Teleost Lineages: Insights into Lipid Metabolism and Xenobiotic Exploitation.

André M. Machado,Isabel Cunha,Raquel Ruivo,Elza Fonseca,Inês Páscoa,Francisca Conrado,Renato Ferraz,Luís Filipe C. Castro

doi:10.3390/genes13010107

Abstract

Three peroxisome proliferator-activated receptor paralogues (PPARα, -β and -γ) are currently recognized in vertebrate genomes. PPARγ is known to modulate nutrition, adipogenesis and immunity in vertebrates. Natural ligands of PPARγ have been proposed; however, the receptor also binds synthetic ligands such as endocrine disruptors. Two paralogues of PPARα and PPARβ have been documented in teleost species, a consequence of the 3R WGD. Recently, two PPARγ paralogue genes were also identified in Astyanax mexicanus. We aimed to determine whether the presence of two PPARγ paralogues is prevalent in other teleost genomes, through genomic and phylogenetic analysis. Our results showed that besides Characiformes, two PPARγ paralogous genes were also identified in other teleost taxa, coinciding with the teleost-specific, whole-genome duplication and with the retention of both genes prior to the separation of the Clupeocephala. To functionally characterize these genes, we used the European sardine (Sardina pilchardus) as a model. PPARγA and PPARγB display a different tissue distribution, despite the similarity of their functional profiles: they are unresponsive to tested fatty acids and other human PPARγ ligands yet yield a transcriptional response in the presence of tributyltin (TBT). This observation puts forward the relevance of comparative analysis to decipher alternative binding architectures and broadens the disruptive potential of man-made chemicals for aquatic species.

Highlights

Nuclear receptors (NRs) are metazoan-specific transcription factors that modulate the expression of target genes involved in multiple aspects of physiological homeostasis e.g., [1,2]
In agreement with the 3R whole-genome duplication (WGD), two branches diverged in the teleost PPARγ group, corresponding to the PPARγ gene duplication in the last common ancestor of teleosts
We examined the relative gene expression (RGE) of the two PPARγ paralogues using the European sardine as a model

Summary

Introduction

Nuclear receptors (NRs) are metazoan-specific transcription factors that modulate the expression of target genes involved in multiple aspects of physiological homeostasis e.g., [1,2]. Among NRs, we find the peroxisome proliferator-activated receptors (PPARα, -β and -γ), which control multiple aspects of lipid metabolism and have been described in vertebrate and invertebrate species [3,4]. PPARα, PPARβ and PPARγ are classical examples of paralogous genes originated from whole-genome duplication (WGD) events that occurred in the vertebrate ancestor. In some invertebrates, such as Saccoglossus kowalevskii (Hemichordata) [5], nonvertebrate chordates (amphioxus (Cephalochordata) and sea squirts (Tunicata)) [5,6], and protostome molluscs [4,7], a single PPAR orthologous gene is found. In the case of PPARγ, a second gene was reported in Astyanax mexicanus (Mexican tetra) [13]

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