Limits...
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.

Show MeSH
Phylogenetic tree of selected vertebrate CES amino acid sequences. Each branch of the tree is labeled with the gene name followed by the species name. Shown is the neighbor joining (NJ) tree based on JTT+gamma corrected distances. Nodes with strong NJ and maximum parsimony (MP) bootstrap support (BSS) and Bayesian posterior probability (BPP) support are highlighted with black and grey dots (see legend at bottom). Black arrows indicate nodes constrained in the MULTIDIVTIME analysis (see Materials and Methods for details). Divergence time estimates (MY) and 95% confidence intervals are given for early branching events that gave rise to the modern CES gene families, and the more recent duplication events that led to the three marsupial CES2 family members.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2266714&req=5

Figure 4: Phylogenetic tree of selected vertebrate CES amino acid sequences. Each branch of the tree is labeled with the gene name followed by the species name. Shown is the neighbor joining (NJ) tree based on JTT+gamma corrected distances. Nodes with strong NJ and maximum parsimony (MP) bootstrap support (BSS) and Bayesian posterior probability (BPP) support are highlighted with black and grey dots (see legend at bottom). Black arrows indicate nodes constrained in the MULTIDIVTIME analysis (see Materials and Methods for details). Divergence time estimates (MY) and 95% confidence intervals are given for early branching events that gave rise to the modern CES gene families, and the more recent duplication events that led to the three marsupial CES2 family members.

Mentions: A phylogenetic tree (Figure 4) was estimated using a progressive alignment of 6 human CES amino acid sequences with the following opossum CES sequences: CES2.1 (derived from sequencing a full-length cDNA); CES1, CES2.2 and CES2.3 (derived from BLAT interrogations of the opossum genome and from sequencing cDNA clones of RT-PCR products for these genes); and CES6 (derived from blat interrogation of the opossum genome using human CES6) [39,40]. We also included other vertebrate CES homologues including chicken, frog and salmon, in addition to two divergent fly sequences as outgroup sequences.


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)

Phylogenetic tree of selected vertebrate CES amino acid sequences. Each branch of the tree is labeled with the gene name followed by the species name. Shown is the neighbor joining (NJ) tree based on JTT+gamma corrected distances. Nodes with strong NJ and maximum parsimony (MP) bootstrap support (BSS) and Bayesian posterior probability (BPP) support are highlighted with black and grey dots (see legend at bottom). Black arrows indicate nodes constrained in the MULTIDIVTIME analysis (see Materials and Methods for details). Divergence time estimates (MY) and 95% confidence intervals are given for early branching events that gave rise to the modern CES gene families, and the more recent duplication events that led to the three marsupial CES2 family members.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Phylogenetic tree of selected vertebrate CES amino acid sequences. Each branch of the tree is labeled with the gene name followed by the species name. Shown is the neighbor joining (NJ) tree based on JTT+gamma corrected distances. Nodes with strong NJ and maximum parsimony (MP) bootstrap support (BSS) and Bayesian posterior probability (BPP) support are highlighted with black and grey dots (see legend at bottom). Black arrows indicate nodes constrained in the MULTIDIVTIME analysis (see Materials and Methods for details). Divergence time estimates (MY) and 95% confidence intervals are given for early branching events that gave rise to the modern CES gene families, and the more recent duplication events that led to the three marsupial CES2 family members.
Mentions: A phylogenetic tree (Figure 4) was estimated using a progressive alignment of 6 human CES amino acid sequences with the following opossum CES sequences: CES2.1 (derived from sequencing a full-length cDNA); CES1, CES2.2 and CES2.3 (derived from BLAT interrogations of the opossum genome and from sequencing cDNA clones of RT-PCR products for these genes); and CES6 (derived from blat interrogation of the opossum genome using human CES6) [39,40]. We also included other vertebrate CES homologues including chicken, frog and salmon, in addition to two divergent fly sequences as outgroup sequences.

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