The Origin and Diversity of Cpt1 Genes in Vertebrate Species

Abstract

The Carnitine palmitoyltransferase I (Cpt1) gene family plays a crucial role in energy homeostasis since it is required for the occurrence of fatty acid β-oxidation in the mitochondria. The exact gene repertoire in different vertebrate lineages is variable. Presently, four genes are documented: Cpt1a, also known as Cpt1a1, Cpt1a2; Cpt1b and Cpt1c. The later is considered a mammalian innovation resulting from a gene duplication event in the ancestor of mammals, after the divergence of sauropsids. In contrast, Cpt1a2 has been found exclusively in teleosts. Here, we reassess the overall evolutionary relationships of Cpt1 genes using a combination of approaches, including the survey of the gene repertoire in basal gnathostome lineages. Through molecular phylogenetics and synteny studies, we find that Cpt1c is most likely a rapidly evolving orthologue of Cpt1a2. Thus, Cpt1c is present in other lineages such as cartilaginous fish, reptiles, amphibians and the coelacanth. We show that genome duplications (2R) and variable rates of sequence evolution contribute to the history of Cpt1 genes in vertebrates. Finally, we propose that loss of Cpt1b is the likely cause for the unusual energy metabolism of elasmobranch.

Molecular characterization and nutritional regulation of carnitine palmitoyltransferase (CPT) family in grass carp (Ctenopharyngodon idellus)

“…Interestingly, the absence of CPT 1γ was discovered in fish species including grass carp. Lopes-Marques et al (2015) reassessed the evolutionary relationships of CPT family and suggested that the first duplication in the ancestor of vertebrates generated CPT 1 and CPT 2, and the second duplication of CPT 1 gene in vertebrates resulted in CPT 1α, CPT 1β, and CPT 1γ. However, the teleost fish lost CPT 1γ, and the chondrichthyes lost CPT 1β as a result of the special energy metabolism among vertebrates (Lopes-Marques et al, 2015).…”

“…Similarly, in fish, the isoforms CPT 1α and CPT 1β were identified and characterized in previous studies on trout and sea bream (Boukouvala et al, 2010;Morash et al, 2008;Morash and McClelland, 2011). Interestingly, teleosts possess multiple isoforms of the CPT gene family, including CPT 1α1a, CPT 1α1b, and CPT 1α2a (Wu et al, 2016;Zheng et al, 2013), which might result from a unique evolutionary history in fish that involves genome duplication (Lopes-Marques et al, 2015;Morash et al, 2010).…”

“…The carnitine palmitoyltransferase system is an essential step in the β-oxidation of long chain fatty acids (Lopes-Marques et al, 2015), because it allows for subsequent movement of the acyl carnitine from the cytosol across the intermembrane space of mitochondria. The carnitine palmitoyltransferase (CPT) family, a mitochondrial transferase enzyme (EC 2.3.1.21) family, plays an indispensable role in fatty acid β-oxidation via catalyzing the conversion of fatty acid-CoAs into fatty acid-carnitines.…”

Partial sequence characterization and ontogenetic expression of genes involved in lipid metabolism in the tropical gar (Atractosteus tropicus)

“…Fatty acid synthase is a multifunctional enzyme that catalyses FA biosynthesis (lipogenesis) in the cytoplasm of adipocytes and hepatocytes (Liu et al, ). Finally, CPT1C is a brain‐specific enzyme involved in the regulation of ketogenesis (production of ketonic bodies during fat metabolism) (Lee & Wolfgang, ; Lopes‐Marques et al, ; McPherson & McEneny, ), and plays a crucial role in ‐oxidation of FA, facilitating the initial step in the transfer of acyl to the mitochondrial matrix (Price et al, ; Toral et al, ).…”

“…Relatively few studies on lipogenic genes in fish address the characterization and tissue‐specific distribution of CPT1; these have been conducted in rainbow trout ( Oncorhynchus mykiss , Walbaum 1792) (Gutierres, Damon, Panserat, Kaushik, & Medale, ) and yellow catfish ( Pelteobagrus fulvidraco , Richardson 1846) (Zheng, Luo, Zhu, Chen, & Gong, ). Additionally, Boukouvala, Leaver, Favre‐Krey, Theodoridou, and Krey () characterized the CPT1B gene based on muscle tissue cDNA in seabream ( Sparus aurata , Linnaeus 1758), and Lopes‐Marques et al () examined the evolutionary history of the CPT1 gene family in vertebrate species, using amino acid (AA) sequences of several fish species under a comparative genomics approach. The molecular characterization and tissue expression of ACC1 gene was determined for grass carp ( Ctenopharyngodon idella , Valenciennes 1844) (Cheng et al, ).…”