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Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor.

Holmes RS, Chan J, Cox LA, Murphy WJ, VandeBerg JL - BMC Evol. Biol. (2008)

Bottom Line: Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and Drosophila CES gene products.Amino acid sequences for opossum CES1 and three CES2 gene products revealed conserved residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization.Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA. rholmes@sfbrgenetics.org

ABSTRACT

Background: Carboxylesterases (CES) perform diverse metabolic roles in mammalian organisms in the detoxification of a broad range of drugs and xenobiotics and may also serve in specific roles in lipid, cholesterol, pheromone and lung surfactant metabolism. Five CES families have been reported in mammals with human CES1 and CES2 the most extensively studied. Here we describe the genetics, expression and phylogeny of CES isozymes in the opossum and report on the sequences and locations of CES1, CES2 and CES6 'like' genes within two gene clusters on chromosome one. We also discuss the likely sequence of gene duplication events generating multiple CES genes during vertebrate evolution.

Results: We report a cDNA sequence for an opossum CES and present evidence for CES1 and CES2 like genes expressed in opossum liver and intestine and for distinct gene locations of five opossum CES genes,CES1, CES2.1, CES2.2, CES2.3 and CES6, on chromosome 1. Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and Drosophila CES gene products. Phylogenetic analyses produced congruent phylogenetic trees depicting a rapid early diversification into at least five distinct CES gene family clusters: CES2, CES1, CES7, CES3, and CES6. Molecular divergence estimates based on a Bayesian relaxed clock approach revealed an origin for the five mammalian CES gene families between 328-378 MYA.

Conclusion: The deduced amino acid sequence for an opossum cDNA was consistent with its identity as a mammalian CES2 gene product (designated CES2.1). Distinct gene locations for opossum CES1 (1: 446,222,550-446,274,850), three CES2 genes (1: 677,773,395-677,927,030) and a CES6 gene (1: 677,585,520-677,730,419) were observed on chromosome 1. Opossum CES1 and multiple CES2 genes were expressed in liver and intestine. Amino acid sequences for opossum CES1 and three CES2 gene products revealed conserved residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.

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Schematic representation of the CES genes on chromosome one of the opossum.
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Figure 3: Schematic representation of the CES genes on chromosome one of the opossum.

Mentions: The predicted amino acid sequence for opossum CES1 showed 63% identity with human CES1 and 46% identity with human CES2 supporting its designation within the CES1 family (Table 2). Opossum CES1 also shared several key residues with human CES1, including the active site 'triad', Ser221, Glu353 and His468 (residue numbers refer to the opossum CES1 sequence); the corresponding cysteine residues forming the disulfide bonds in human CES1 (Cys87/Cys116 and Cys273/Cys284); the microsomal C-terminus retention sequence His-Ile-Glu-Leu (HIEL); and the high-mannose N-linked glycosylation site at Asn190-X-Thr. Two other potential glycosylation sites (257Asn-Ser-Ser and 528Asn-Ile-Thr) were also observed for the opossum CES1 sequence (Fig. 3). The N-terminal microsomal signal peptide for human CES1, which retains the enzyme within the ER [12] was identical in sequence with the predicted opossum CES1 sequence, and both sequences retain 18 homologous residues in corresponding positions.


Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor.

Holmes RS, Chan J, Cox LA, Murphy WJ, VandeBerg JL - BMC Evol. Biol. (2008)

Schematic representation of the CES genes on chromosome one of the opossum.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2266714&req=5

Figure 3: Schematic representation of the CES genes on chromosome one of the opossum.
Mentions: The predicted amino acid sequence for opossum CES1 showed 63% identity with human CES1 and 46% identity with human CES2 supporting its designation within the CES1 family (Table 2). Opossum CES1 also shared several key residues with human CES1, including the active site 'triad', Ser221, Glu353 and His468 (residue numbers refer to the opossum CES1 sequence); the corresponding cysteine residues forming the disulfide bonds in human CES1 (Cys87/Cys116 and Cys273/Cys284); the microsomal C-terminus retention sequence His-Ile-Glu-Leu (HIEL); and the high-mannose N-linked glycosylation site at Asn190-X-Thr. Two other potential glycosylation sites (257Asn-Ser-Ser and 528Asn-Ile-Thr) were also observed for the opossum CES1 sequence (Fig. 3). The N-terminal microsomal signal peptide for human CES1, which retains the enzyme within the ER [12] was identical in sequence with the predicted opossum CES1 sequence, and both sequences retain 18 homologous residues in corresponding positions.

Bottom Line: Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and Drosophila CES gene products.Amino acid sequences for opossum CES1 and three CES2 gene products revealed conserved residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization.Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA. rholmes@sfbrgenetics.org

ABSTRACT

Background: Carboxylesterases (CES) perform diverse metabolic roles in mammalian organisms in the detoxification of a broad range of drugs and xenobiotics and may also serve in specific roles in lipid, cholesterol, pheromone and lung surfactant metabolism. Five CES families have been reported in mammals with human CES1 and CES2 the most extensively studied. Here we describe the genetics, expression and phylogeny of CES isozymes in the opossum and report on the sequences and locations of CES1, CES2 and CES6 'like' genes within two gene clusters on chromosome one. We also discuss the likely sequence of gene duplication events generating multiple CES genes during vertebrate evolution.

Results: We report a cDNA sequence for an opossum CES and present evidence for CES1 and CES2 like genes expressed in opossum liver and intestine and for distinct gene locations of five opossum CES genes,CES1, CES2.1, CES2.2, CES2.3 and CES6, on chromosome 1. Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and Drosophila CES gene products. Phylogenetic analyses produced congruent phylogenetic trees depicting a rapid early diversification into at least five distinct CES gene family clusters: CES2, CES1, CES7, CES3, and CES6. Molecular divergence estimates based on a Bayesian relaxed clock approach revealed an origin for the five mammalian CES gene families between 328-378 MYA.

Conclusion: The deduced amino acid sequence for an opossum cDNA was consistent with its identity as a mammalian CES2 gene product (designated CES2.1). Distinct gene locations for opossum CES1 (1: 446,222,550-446,274,850), three CES2 genes (1: 677,773,395-677,927,030) and a CES6 gene (1: 677,585,520-677,730,419) were observed on chromosome 1. Opossum CES1 and multiple CES2 genes were expressed in liver and intestine. Amino acid sequences for opossum CES1 and three CES2 gene products revealed conserved residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.

Show MeSH