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The Origin and Diversity of Cpt1 Genes in Vertebrate Species.

Lopes-Marques M, Delgado IL, Ruivo R, Torres Y, Sainath SB, Rocha E, Cunha I, Santos MM, Castro LF - PLoS ONE (2015)

Bottom Line: 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.Finally, we propose that loss of Cpt1b is the likely cause for the unusual energy metabolism of elasmobranch.

View Article: PubMed Central - PubMed

Affiliation: CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, CIMAR Associate Laboratory, UPorto-University of Porto, Porto, Portugal; ICBAS, Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal.

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.

No MeSH data available.


Schematic representation of two evolutionary scenarios of Cpt1 genes.Model 1 derived from Morash et al. 2010 [9], and Model 2 derived from Ka et al. 2013 [8].
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pone.0138447.g005: Schematic representation of two evolutionary scenarios of Cpt1 genes.Model 1 derived from Morash et al. 2010 [9], and Model 2 derived from Ka et al. 2013 [8].

Mentions: The conversion of long chain fatty acids into acylcarnitines, a fundamental step in the transport of long chain fatty acids to the mitochondria for β-oxidation, is catalyzed by CPT1. Thus, this enzyme plays an essential role in energy homeostasis, since it regulates fatty acid import for subsequent oxidation. Here, we set out to reassess the evolutionary history of Cpt1 genes in vertebrate history, paying special attention to a basal gnathostome lineage, the chondrichthyans. These are known to have an unusual energetic metabolism without fatty acid oxidation in both skeletal and cardiac muscle [24]. Additionally, Cpt1c a so-called mammalian specific gene has an unclear origin and function. Several evolutionary models have been put forward to account for the reported Cpt1 gene diversity in vertebrate lineages (Fig 5). Morash and co-workers (2010) proposed that a duplication in the ancestor of both fish and mammals gave rise to the Cpt1a and Cpt1b isoforms [9], (Fig 5 model 1), with a subsequent duplication generating Cpt1a1 and Cpt1a2 isoforms after the divergence of teleost fish; in an alternative scenario the 1a2 isoform was secondarily lost in mammals while retained in teleosts [9]. Extra specific genome duplications that took place in teleosts (e.g. 3R and 4R) would be responsible for the higher number of Cpt1 genes in fish species (e.g. Cpt1a1a and Cpt1a1b) [9]. Nevertheless, this proposal did not address the origin and evolution of the puzzling Cpt1c gene, nor did it provide clear insight into the duplication history of Cpt1a1 and Cpt1a2 genes. So far, Cpt1c has been largely recognized as a mammalian novelty with no orthologues identified in non-mammalian genomes [7, 25]. On the basis of phylogenetics and chromosomal mapping of the G. gallus Cpt1b gene, it was proposed that Cpt1c and Cpt1b emerged in mammalian ancestry from the duplication of a Cpt1b/c gene after the divergence of sauropsids (Fig 5 model 2) [8]. Thus, the sauropsid Cpt1b would be pro-orthologous of mammalian Cpt1b and Cpt1c [8].


The Origin and Diversity of Cpt1 Genes in Vertebrate Species.

Lopes-Marques M, Delgado IL, Ruivo R, Torres Y, Sainath SB, Rocha E, Cunha I, Santos MM, Castro LF - PLoS ONE (2015)

Schematic representation of two evolutionary scenarios of Cpt1 genes.Model 1 derived from Morash et al. 2010 [9], and Model 2 derived from Ka et al. 2013 [8].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589379&req=5

pone.0138447.g005: Schematic representation of two evolutionary scenarios of Cpt1 genes.Model 1 derived from Morash et al. 2010 [9], and Model 2 derived from Ka et al. 2013 [8].
Mentions: The conversion of long chain fatty acids into acylcarnitines, a fundamental step in the transport of long chain fatty acids to the mitochondria for β-oxidation, is catalyzed by CPT1. Thus, this enzyme plays an essential role in energy homeostasis, since it regulates fatty acid import for subsequent oxidation. Here, we set out to reassess the evolutionary history of Cpt1 genes in vertebrate history, paying special attention to a basal gnathostome lineage, the chondrichthyans. These are known to have an unusual energetic metabolism without fatty acid oxidation in both skeletal and cardiac muscle [24]. Additionally, Cpt1c a so-called mammalian specific gene has an unclear origin and function. Several evolutionary models have been put forward to account for the reported Cpt1 gene diversity in vertebrate lineages (Fig 5). Morash and co-workers (2010) proposed that a duplication in the ancestor of both fish and mammals gave rise to the Cpt1a and Cpt1b isoforms [9], (Fig 5 model 1), with a subsequent duplication generating Cpt1a1 and Cpt1a2 isoforms after the divergence of teleost fish; in an alternative scenario the 1a2 isoform was secondarily lost in mammals while retained in teleosts [9]. Extra specific genome duplications that took place in teleosts (e.g. 3R and 4R) would be responsible for the higher number of Cpt1 genes in fish species (e.g. Cpt1a1a and Cpt1a1b) [9]. Nevertheless, this proposal did not address the origin and evolution of the puzzling Cpt1c gene, nor did it provide clear insight into the duplication history of Cpt1a1 and Cpt1a2 genes. So far, Cpt1c has been largely recognized as a mammalian novelty with no orthologues identified in non-mammalian genomes [7, 25]. On the basis of phylogenetics and chromosomal mapping of the G. gallus Cpt1b gene, it was proposed that Cpt1c and Cpt1b emerged in mammalian ancestry from the duplication of a Cpt1b/c gene after the divergence of sauropsids (Fig 5 model 2) [8]. Thus, the sauropsid Cpt1b would be pro-orthologous of mammalian Cpt1b and Cpt1c [8].

Bottom Line: 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.Finally, we propose that loss of Cpt1b is the likely cause for the unusual energy metabolism of elasmobranch.

View Article: PubMed Central - PubMed

Affiliation: CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, CIMAR Associate Laboratory, UPorto-University of Porto, Porto, Portugal; ICBAS, Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal.

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.

No MeSH data available.